Proteins aggregation and structural protein aggregation amyloid. Medical search. Frequent questions

To understand the mechanism of the aggregation between two types of protein, it is necessary to probe and characterize the molecular interactions between oligomers of these proteins. (neurodegenerationresearch.eu)
To better understand the role of CsgE in curli formation, we have determined the solution NMR structure of a double mutant of CsgE (W48A/F79A) that appears to be similar to the wild-type (WT) protein in overall structure and function but does not form mixed oligomers at NMR concentrations similar to the WT. (wustl.edu)
Polymorphism in the structure of fibrils formed by aggregation suggests the existence of many different assembly pathways and therefore a heterogeneous ensemble of soluble oligomers. (biorxiv.org)
Characterization of this heterogeneity is the key to understanding the aggregation mechanism and toxicity of specific oligomers, but in practice it is extremely difficult because oligomers cannot be readily separated. (biorxiv.org)
Although fibrils are known to be toxic, a number of experimental studies also suggest that a subset of soluble oligomers, transiently appearing during the aggregation process, are more responsible for disease pathology than the fibril itself 2 - 6 . (biorxiv.org)
Despite tremendous effort to understand aggregation of Aβ to form oligomers and fibrils, experimental results vary widely and there is no consensus on the model for these processes 7 . (biorxiv.org)
In this initial study, we combine single-molecule Förster resonance energy transfer (FRET) spectroscopy, fluorescence lifetime imaging (FLIM), and image analysis using deep learning (codes are available at https://github.com/hoisunglab/FNet ) to interrogate several steps during the aggregation process of the 42-residue Aβ peptide (Aβ42), including dimerization, formation of stable oligomers, and fibril elongation. (biorxiv.org)
The amyloid protein aggregation associated with diseases such as Alzheimer's, Parkinson's and type II diabetes (among many others) features a bewildering variety of β-sheet-rich structures in transition from native proteins to ordered oligomers and fibres. (cornell.edu)
Before forming such filaments, proteins undergo an intermediate stage, the oligomers, which are also present in the brains of Parkinson's patients. (sciencedaily.com)
However, there is no consensus on what mechanisms trigger aggregation, neuronal cell loss, and degeneration, neither how toxic the aggregates and the oligomers are to the cells. (sciencedaily.com)
Then, they observed significant differences in the aggregation processes of each protein and found that oligomers develop at a much greater rate in early onset cases than in aging cases of Parkinson. (sciencedaily.com)
The structural and biochemical details of these oligomers have been largely unknown. (cornell.edu)
p53 aggregates are heterogeneous assemblies composed of amorphous aggregates, oligomers, and amyloid-like fibrils. (bvsalud.org)
While these compounds did not reduce the amount of protein aggregates, they were found to reduce the protein's toxicity and to increase the stability of amyloid fibrils - a finding that lends further evidence to the theory that smaller assemblies of amyloid-beta known as oligomers, and not the fibrils themselves, are the toxic agents responsible for Alzheimer's symptoms. (uclahealth.org)
The researchers hypothesize that by binding snugly to the protein, the compounds they identified may be preventing these smaller oligomers from breaking free of the amyloid-beta fibrils, thus keeping toxicity in check. (uclahealth.org)
The purified protein is well folded and composed of oligomers with a varying number of subunits according to small-angle X-ray scattering (SAXS). (lu.se)
Amyloid fibrils are made of normally soluble misfolded proteins that aggregate into oligomers and then insoluble fibrils. (msdmanuals.com)
However, some prefibrillar oligomers of amyloidogenic proteins have direct cellular toxicity, an important component of disease pathogenesis. (msdmanuals.com)

Protein aggregates in neurons are characteristic for Alzheimer's, Parkinson's and other neurodegenerative diseases. (unibas.ch)
Mutant vasopressin forms pathological protein aggregates (red) instead of natural granules (green) in the nerve cells. (unibas.ch)
Also in the case of the hormone vasopressin, only the negative effects of such protein aggregates have been recognized so far: Mutations in the vasopressin gene prevent the correct folding of the defective hormone causing it to be retained in the secretory pathway. (unibas.ch)
These are amyloid-like protein aggregates that are physiologically important. (unibas.ch)
Harmful protein aggregates produced by defective proteins appear to be an adverse result of the ability to form granules. (unibas.ch)
The researchers further plan to clarify the effects of vasopressin at the structural level and whether protein aggregates reflect a general principle of granule formation. (unibas.ch)
The variation in the amino-acid sequences of the β-structures presents a challenge to developing a model system of β-sheets for the study of various amyloid aggregates. (cornell.edu)
We have tailored these amyloid β-sheet mimics (ABSMs) to antagonize the aggregation of various amyloid proteins, thereby reducing the toxicity of amyloid aggregates. (cornell.edu)
Biochemical, biophysical and biological assays using isolated amyloid β peptide, primary neurons and various established Alzheimer's disease nematode models showed that the selected macrocycles potently inhibit the formation of neurotoxic amyloid β peptide aggregates. (nature.com)
A number of human neurodegenerative diseases, including Alzheimer"s and Parkinson"s diseases (PD), are associated with the deposition of proteinaceous aggregates known as amyloid fibrils. (uni-goettingen.de)
Researchers haveidentified for the first time the initial steps of alpha-synuclein protein aggregates related to early onsets of hereditary Parkinson cases. (sciencedaily.com)
For the first time, scientists observed how variants of the Parkinson's disease-associated protein alpha-synuclein change over time and were able to identify the initial stages of protein aggregates linked to early onset of familial cases of the disease. (sciencedaily.com)
It is already known that the degeneration of neurons leading to the onset of symptoms such as tremors is linked to alpha-synuclein aggregates, also called amyloid filaments, in the brain. (sciencedaily.com)
The intermediate structures and the amyloid aggregates accumulate over time in the brain. (sciencedaily.com)
The pathophysiology of prion-like diseases involves the structural transformation of wild-type (wt) proteins to transmissible forms that can convert healthy proteins, generating aggregates. (bvsalud.org)
The unfolded amyloid CsgA, which is secreted by bacteria and later aggregates extracellularly to create biofilms, mediates adherence to epithelial cells, and aids in bacteriophage defense, forms the curli fibers. (standardofcare.com)
However, the mechanism of formation and the structural and functional properties of aggregates formed from these three peptides are different in such a way that they do not cross-seed each other despite sharing a common amino acid composition. (ibecbarcelona.eu)
Alpha-synuclein is found in healthy cells in the nervous system, but problems arise when it clumps together, or aggregates, into plaques known as amyloid that can disrupt normal function. (leeds.ac.uk)
When the control regions were deleted in the worms, alpha-synuclein no longer formed aggregates, and the worms were healthier and more mobile, even in old age, compared to worms expressing the normal alpha-synuclein protein. (leeds.ac.uk)
The inherent tendency of proteins to convert from their native states into amyloid aggregates is associated with a range of human disorders, including Alzheimer's and Parkinson's diseases. (mpg.de)
We also report a transient accumulation of pre-fibrillar aggregates, likely to be a result of heavily saturated secondary nucleation, which can form a basis for further structural studies of this phenomenon. (lu.se)

One major research focus is the role of protein misfolding in the onset of amyloidogenic diseases, including dialysis-related amyloidosis, Alzheimer's and Type II diabetes. (wikipedia.org)
Bourgade K, Garneau H, Giroux G, Le Page AY, Bocti C, Dupuis G, Frost EH, Fülöp T Jr . β-Amyloid peptides display protective activity against the human Alzheimer's disease-associated herpes simplex virus-1 . (alzforum.org)
Recent advances suggest that an age-related decline in proteostasis capacity allows the manifestation of various protein-aggregation diseases, including Alzheimer's disease and Parkinson's disease. (nature.com)
Protein aggregation is implicated as the cause of pathology in various diseases such as Alzheimer's and Parkinson's disease. (biorxiv.org)
Its aggregation to form fibrils that are found in brain tissue is one of the key characteristics of Alzheimer's disease. (biorxiv.org)
We describe the structures and inhibitory properties of ABSMs containing amyloidogenic peptides from the amyloid-β peptide associated with Alzheimer's disease, β(2)-microglobulin associated with dialysis-related amyloidosis, α-synuclein associated with Parkinson's disease, islet amyloid polypeptide associated with type II diabetes, human and yeast prion proteins, and Tau, which forms neurofibrillary tangles. (cornell.edu)
Protein misfolding and aggregation are common pathological features of several human diseases, including Alzheimer's disease and type 2 diabetes. (nature.com)
We demonstrate the effectiveness of this approach by identifying drug-like, head-to-tail cyclic peptides that modulate the aggregation of the Alzheimer's disease-associated amyloid β peptide. (nature.com)
Other polypeptides and proteins , such as amylin and the Alzheimer's beta protein do not have a simple consensus sequence and are thought to operate by hydrophobic association. (wikidoc.org)
The increased spectral resolution and sensitivity of the 1.2 GHz NMR has already enabled research teams to look more deeply at proteins and better understand the initial steps of amyloid-type protein aggregation as well as the function and structure of the Tau protein, both commonly associated with Alzheimer's disease. (bruker.com)
The most commonly known amyloid diseases are Alzheimer's, Parkinson's, and Transmissible Spongiform Encephalopathies (TSEs). (bvsalud.org)
Aggregation of extracellular amyloid-β (Aβ) is thought to play a major part in the pathogenesis of Alzheimer's disease. (axonmedchem.com)
Caprospinol reduces amyloid deposits and improves cognitive function in a rat model of Alzheimer's disease. (axonmedchem.com)
While the GI tract has been linked to other neurological disorders such autism spectrum disorder, depression, anxiety, and Alzheimer's disease, protein aggregation and/or inflammation in the gut represents synucleinopathies. (standardofcare.com)
The stacked gray arrows are a artistic representations of the amyloid proteins associated with numerous diseases, including Alzheimer's. (uclahealth.org)
The UCLA researchers, led by David Eisenberg, director of the UCLA-Department of Energy Institute of Genomics and Proteomics and a Howard Hughes Medical Institute investigator, report the first application of this technique in the search for molecular compounds that bind to and inhibit the activity of the amyloid-beta protein responsible for forming dangerous plaques in the brain of patients with Alzheimer's and other degenerative diseases. (uclahealth.org)
Their research is focused on the development of new treatments for diseases caused by protein aggregation, including Alzheimer's disease and transthyretin amyloidosis. (researchoutreach.org)

The three IAPP peptides readily aggregate into ordered, Î²-sheet-enriched, amyloid-like fibrils. (ibecbarcelona.eu)
A peptide is smaller than a protein - peptides are made of up to 50 amino acids (over 50 amino acids gives you a protein). (researchoutreach.org)
The structure of the oligomer with the S/T-rich region is a large step forward in the understanding of the function of DNAJB6 and how it can bind aggregation-prone peptides and prevent amyloid diseases. (lu.se)

Influence of aggregation propensity and stability on amyloid fibril formation as studied by Fourier transform infrared spectroscopy and two-dimensional COS analysis. (nih.gov)
Here, we investigate highly heterogeneous oligomerization and fibril formation of the 42-residue amyloid-β peptide (Aβ42). (biorxiv.org)
Small molecule inhibitors of islet amyloid polypeptide fibril formation. (jnu.ac.in)
Inhibiting the islet amyloid polypeptide fibril formation by the red wine compound resveratrol. (jnu.ac.in)
NMR spectroscopic investigation of early events in IAPP amyloid fibril formation. (jnu.ac.in)
The tight sequence/structure relationship governing protein folding does not seem to apply to amyloid fibril formation because many proteins without any sequence relationship have been shown to assemble into very similar Î²-sheet-enriched structures. (ibecbarcelona.eu)
Binding modes of phthalocyanines to amyloid β peptide and their effects on amyloid fibril formation. (mpg.de)
The remarkably efficient suppression of amyloid fibril formation by the DNAJB6 chaperone is dependent on a set of conserved S/T-residues and an oligomeric structure, features unusual among DNAJ chaperones. (lu.se)

All of these diseases are marked by harmful, elongated, rope-like structures known as amyloid fibrils, linked protein molecules that form in the brains of patients. (uclahealth.org)
Amyloidosis is a group of rare but serious conditions caused when deposits of damaged proteins known as amyloid fibrils, accumulate around tissues and organs. (researchoutreach.org)

APOE binds to cell-surface receptors to deliver lipids and to the hydrophobic amyloid-β peptide, regulating amyloid-β aggregations and clearances in the brain. (dovepress.com)
Arguelles J, Lee J, Cardenas LV, Govind S, Singh S. In Silico Analysis of a Drosophila Parasitoid Venom Peptide Reveals Prevalence of the Cation-Polar-Cation Clip Motif in Knottin Proteins. (cuny.edu)
Amyloid-β (Aβ) is a peptide fragment consisting of 39 - 43 amino acid residues, which is produced by successive proteolytic cleavages of the amyloid precursor protein (APP) 1 . (biorxiv.org)
Amyloid plaques form when levels of the monomeric, soluble Aβ peptide build up in the extracellular interstitial fluid (ISF) in the brain. (axonmedchem.com)
Here, we have characterized the aggregation kinetics, seeding ability, morphology, conformation, stability, and toxicity of amyloid fibrils formed by a 20-residue domain of the islet amyloid polypeptide (IAPP), as well as of a backward and scrambled version of this peptide. (ibecbarcelona.eu)
We present here the structural characterization of the binding of PcTS and its Cu(II) and Zn(II)-loaded forms to the amyloid β-peptide (Aβ) and the impact of these interactions on the peptide amyloid fibril assembly. (mpg.de)
Our results demonstrated that formation of the Aβ40-PcTS complex does not interfere with the progression of the peptide toward the formation of amyloid fibrils. (mpg.de)
While the aggregation of the amyloid β peptide (Aβ) into amyloid fibrils is highly implicated as a key factor in the disease, the molecular nature of its involvement has proven complex and elusive. (lu.se)

Patients may also present with atrial arrhythmias or conduction system disease due to amyloid fibril deposition within areas responsible for electrical impulse conduction. (medscape.com)
Biopsy of an organ with impaired function (eg, heart, GI tract) can definitively establish a cause-and-effect relationship between organ dysfunction and amyloid deposition. (medscape.com)
We respectfully point out that a central finding of our previous study is that HSV1 (and other pathogens) directly seed amyloid deposition as a mechanism to trap and neutralize invading microbes. (alzforum.org)
To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. (elifesciences.org)
Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. (elifesciences.org)
Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner. (elifesciences.org)
Amyloidosis is a group of diseases characterized by abnormal aggregation of proteins to form amyloid fibrils, and subsequent deposition in various tissues and organs, which can lead to severe functional failures. (elifesciences.org)
We are interested in the relationship between beta-amyloid deposition and the progressive formation of dystrophic neurites and cell death in hippocampal neurons. (northwestern.edu)
TTR amyloidosis (ATTR) is a progressive, fatal disease in which deposition of amyloid derived from either mutant or wild-type TTR causes severe organ damage and dysfunction. (researchoutreach.org)
Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. (msdmanuals.com)
Localized forms of amyloidosis appear to be caused by local production and deposition of an amyloidogenic protein (most often immunoglobulin light chains) within the affected organ rather than by deposition of circulating proteins. (msdmanuals.com)

In in vitro experiments, curcumin has been shown to suppress the aggregation and cytotoxicity of Aβ, αSyn, islet amyloid precursor protein, ATTR, and prion protein ( Stefani and Rigacci, 2013 ). (elifesciences.org)
Type 2 Diabetes Mellitus is one of these protein misfolding disorders and involves human islet amyloid polypeptide misfolding and accumulating in parts of the body, primarily in the pancreas causing damage to islet cells and affecting glucose regulation. (londonmet.ac.uk)

These solid, insoluble protein clumps damage the nerve cells. (unibas.ch)
This results in the formation of insoluble protein amyloids, which destroy the vasopressin producing neurons in the brain. (unibas.ch)
Amyloids are insoluble fibrous protein aggregations sharing specific structural traits. (wikidoc.org)
The aggregation cascade of disease-related amyloidogenic proteins, terminating in insoluble amyloid fibrils, involves intermediate oligomeric states. (cornell.edu)
Silks have evolved specifically to readily form insoluble ordered structures with a wide range of structural functionality. (ox.ac.uk)
Amyloid deposits are composed of small (about 10 nm diameter), insoluble fibrils that form congophilic beta-pleated sheets that can be identified by x-ray diffraction. (msdmanuals.com)

her nomination reads: Sheena Radford is internationally distinguished for her seminal contributions to understanding how the dynamical properties of proteins enable them to fold and function biologically, or to misfold and cause degenerative diseases. (wikipedia.org)
Understanding the mutations in APOE, their structural properties, and their isoforms is important to determine its role in various diseases and to advance the development of therapeutic strategies. (dovepress.com)
Protein aggregation is associated with numerous incurable diseases, including A? (neurodegenerationresearch.eu)
The output of this project will be a detailed description of the interactions between proteins that are related to neurodegenerative diseases. (neurodegenerationresearch.eu)
Moreover, this proposal may provide insight into the link between AD and PD, and will pave the way to the development of potential drugs to alleviate/prevent the symptoms of neurodegenerative diseases by impending/preventing the interaction between the proteins. (neurodegenerationresearch.eu)
Understanding curli formation can provide the information necessary to develop treatments and therapeutic agents for biofilm-related infections and may benefit the prevention and treatment of amyloid diseases. (wustl.edu)
In the past, amyloids have mainly been associated with neurodegenerative diseases. (unibas.ch)
In neurodegenerative diseases, amyloids cause damage and death of neurons. (unibas.ch)
They are also prone to aggregation, a phenomena which has been implicated for many diseases (the so-called misfolding and amyloid diseases). (berkeley.edu)
Disruption of this transport and alterations in the structural proteins often lead to protein aggregation and intracellular inclusions associated with neurodegenerative diseases. (northwestern.edu)
Structure-based drug design, in which the physical structure of a targeted protein is used to help identify compounds that will interact with it, has already been used to generate therapeutic agents for a number of infectious and metabolic diseases. (uclahealth.org)
Investigator Professor Sheena Radford, FMedSci FRS, Director of the Astbury Centre for Structural Molecular Biology at the University of Leeds, said: "In trying to tackle diseases like Parkinson's, the first problem is identifying the key areas to target with small-molecules or protein-based medicines, as these proteins do not have a fixed structure, ruling out traditional methods of structure-based drug design. (leeds.ac.uk)
The self-association of prion protein (PrP) is a critical step in the pathology of prion diseases. (bbk.ac.uk)

A number of non-structural screening attempts have been made to identify natural and synthetic compounds that might prevent the aggregation and toxicity of amyloid fibrils. (uclahealth.org)

She has used sophisticated experimental techniques to characterise protein folding pathways in exquisite detail, in particular demonstrating that non-native as well as native-like interactions can play key roles in stabilising partially folded intermediate states. (wikipedia.org)
Until recently, researchers have been unable to replicate the exact tau structures found in vivo , as buffer conditions in vitro often fail to mimic the cellular environment, and fragments do not always follow the same aggregation pathways as the full-length protein. (technologynetworks.com)
The long-term research goal of the lab is to apply computer modeling to gain insight into cellular signal transduction pathways, specifically to provide deeper insight into both the normal and aberrant subcellular targeting of domains contained in proteins which are part of macromolecular complexes and function in various biological processes. (cuny.edu)
Due to the lack of quantitative experimental results, there is no comprehensive aggregation model that includes heterogeneity of aggregation pathways. (biorxiv.org)
p53C exhibited marginal unfolding cooperativity, which could be modulated from unfolding to aggregation pathways with chemical or physical forces. (bvsalud.org)

She has built on these findings to define key steps in the aberrant self-assembly of misfolded proteins into amyloid fibrils, particularly in dialysis related amyloidosis, and to relate these molecular processes to pathogenesis. (wikipedia.org)
Mutated transthyretin is associated with the formation of amyloid fibrils, leading to the development of TTR-related amyloidosis (ATTR). (medscape.com)
Cardiac amyloidosis, which is commonly caused by aggregation of immunoglobulin light chain (AL) or transthyretin (TTR), is a main contributor of morbidity and mortality in patients with amyloidosis. (researchoutreach.org)
A number of normal (wild-type) and mutant proteins are susceptible to such misfolding and aggregation (amyloidogenic proteins), thus accounting for the wide variety of causes and types of amyloidosis. (msdmanuals.com)
For amyloidosis to develop, in addition to production of amyloidogenic proteins, there is probably also a failure of the normal clearance mechanisms for such misfolded proteins. (msdmanuals.com)
In systemic amyloidosis, circulating amyloidogenic proteins form deposits in a variety of organs. (msdmanuals.com)
Amyloidosis caused by aggregation of beta-2-microglobulin can occur in patients on long-term hemodialysis, but the incidence has declined with use of modern high-flow dialysis membranes. (msdmanuals.com)

Here, perturbation of the p53 core domain (p53C) with subdenaturing concentrations of guanidine hydrochloride and high hydrostatic pressure revealed native-like molten globule (MG) states, a subset of which were highly prone to amyloidogenic aggregation. (bvsalud.org)
Prion-like behavior of several amyloidogenic proteins has been demonstrated in recent years. (bvsalud.org)
the amyloidogenic protein is typed using a variety of immunohistologic and biochemical techniques. (msdmanuals.com)

Zhou, W. , Richmond-Buccola, D. , Wang, Q. , and Kranzusch, P. J. (2022) Structural basis of human TREX1 DNA degradation and autoimmune disease . (cornell.edu)

Here, we introduce a family of robust β-sheet macrocycles that can serve as a platform to display a variety of heptapeptide sequences from different amyloid proteins. (cornell.edu)

the mechanism through which the protein pairs aggregate remains controversial. (neurodegenerationresearch.eu)
We suggest a structural mechanism of the interaction between CsgE and CsgA. (wustl.edu)
Molecular modeling and computational analyses suggests that the Sinorhizobium meliloti periplasmic regulator protein ExoR adopts a superhelical fold and is controlled by a unique mechanism of proteolysis. (cuny.edu)
To better understand the pathogenic mechanism, therefore, it is important to characterize the entire aggregation process from the initial oligomerization to the formation and growth of fibrils. (biorxiv.org)
Other projects in the lab focus on the mechanism of protein misfolding, the structural and energetic mechanism of signaling, computational identification of folding modules, and the role of ligand binding. (berkeley.edu)
Our studies on the mechanism of folding include investigating the role of topological complexity using permuted proteins, the nature and function of folding intermediates, and studies on the role of mechanical unfolding using single molecule measurements. (berkeley.edu)
In that sense, the use of small molecules as probes for the structural and toxic mechanism related to amyloid aggregation has become an active area of research. (mpg.de)
Even so, this suggests a ubiquitous aggregation mechanism in which the protein environment is at least as important as the sequence. (ox.ac.uk)
Here we review fiber formation and its prerequisites, and discuss the mechanism by which the animal facilitates and modulates silk assembly to achieve controlled protein aggregation. (ox.ac.uk)
This thesis and the work herein is part of an ongoing effort to map out the aggregation mechanism of Aβ in vitro in as much detail as possible, in the hope to provide a better basis for understanding its role in disease. (lu.se)

Sheena Elizabeth Radford OBE FRS FMedSci is a British biophysicist, and Astbury Professor of Biophysics in the Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology at the University of Leeds. (wikipedia.org)
She became the Deputy Director of the Astbury Centre for Structural Molecular Biology in 2009 then Director in 2012. (wikipedia.org)
Her nomination reads: Sheena Radford is Professor of Structural Molecular Biology at the University of Leeds. (wikipedia.org)
To avoid these dangers, cells invest in a complex network of molecular chaperones, which use ingenious mechanisms to prevent aggregation and promote efficient folding. (nature.com)
Hartl, F. U. Molecular chaperones in cellular protein folding. (nature.com)
The challenge and the focus of this proposal are to identify the specific interactions between these protein pairs and to probe the oligomeric structures of the proteins at the molecular level. (neurodegenerationresearch.eu)
While tauopathies can easily be identified post-mortem by the presence of tangles in brain cells, current structural biology research seeks to understand the formation of individual filaments at the molecular level. (technologynetworks.com)
Surprisingly, proteins with very different amino acid sequences and three-dimensional structures aggregate into amyloid fibrils that share common characteristics, such as a similar morphology and a specific beta-sheet-based molecular architecture. (uni-goettingen.de)
Whereas there is increasing knowledge about the factors that drive aggregation, the structural characteristics of intermediates and the molecular details that determine the arrangement of misfolded prote! (uni-goettingen.de)
Novel GHz-class NMR technology enables advanced research into the structural basis for affinity and specificity of protein-ligand interactions, including a better understanding of structural features of cell membrane proteins, and the molecular mechanisms involved in protein folding and aggregation. (bruker.com)
The finding, made by scientists from the University of Leeds' Astbury Centre for Structural Molecular Biology , provides a new target for the development of therapies to try and slow down or even prevent the disease. (leeds.ac.uk)
Their findings are published today in Nature Structural and Molecular Biology . (leeds.ac.uk)
Compared with other compounds, the structural and molecular basis behind the inhibitory interaction of phthalocyanine tetrasulfonate (PcTS) with proteins such as αS and tau has been well established, contributing to a better understanding of the amyloid aggregation process in these proteins. (mpg.de)
The animal, be it silkworm or spider, will produce, store, and transport high molecular weight proteins in a complex environment to eventually allow formation of silk fibers with a variety of mechanical properties. (ox.ac.uk)

This has been done with the use of native mass spectrometry, NMR and single molecule methods to characterize intermediates of protein folding and in amyloid formation. (wikipedia.org)
Because the formation of amyloid fibrils is nearly irreversible, maintaining proteostasis and inhibiting amyloid aggregation present a challenge for development of an effective treatment. (elifesciences.org)
APOE is also involved in the formation of chylomicrons and VLDL and affects the activity of other lipid metabolism-associated proteins and enzymes, such as hepatic lipase and lipoprotein lipase. (dovepress.com)
Curli, consisting primarily of major structural subunit CsgA, are functional amyloids produced on the surface of Escherichia coli, as well as many other enteric bacteria, and are involved in cell colonization and biofilm formation. (wustl.edu)
Ultimately, an effective treatment will likely require a clear understanding of initial protein misfolding down to the formation of the filamentous tangles. (technologynetworks.com)
They were able to identify two sequences in vasopressin, which in the mutant protein drive the formation of harmful amyloids. (unibas.ch)
By plunge freezing these samples and acquiring advanced electron microscope images, we are able to better understand these wrong protein associations in their native environment and ways to avoid their formation. (sciencedaily.com)
Our research is focused on a quantitative description of protein amyloid formation. (lu.se)
Such studies have revealed that polyphenols, naturally occurring compounds found in green tea and in the spice turmeric, can inhibit the formation of amyloid fibrils. (uclahealth.org)
In this study, researchers Dr Ciaran Doherty and PhD researcher Sabine Ulamec from the Astbury Centre at Leeds, found that two regions outside of NAC play a critical role in controlling amyloid formation of alpha-synuclein. (leeds.ac.uk)
Elucidation of the PcTS binding modes to Aβ40 revealed the involvement of specific aromatic and hydrophobic interactions in the formation of the Aβ40-PcTS complex, ascribed to a binding mode in which the planarity and hydrophobicity of the aromatic ring system in the phthalocyanine act as main structural determinants for the interaction. (mpg.de)

Intestinal dysbiosis may be a major factor in the development of Parkinson's disease by encouraging intestinal permeability, gastrointestinal inflammation, and the aggregation and spread of aSyn. (standardofcare.com)
The etiology of Parkinson's disease (PD) is linked with cellular inclusions in the substantia nigra pars compacta region of the brain that are enriched in the misfolded presynaptic protein α -synuclein ( α S) and death of the dopaminergic neurons. (hindawi.com)
A master control region of a protein linked to Parkinson's disease has been identified for the first time. (leeds.ac.uk)
The study focused on a protein called alpha-synuclein, which is linked to the onset and progression of Parkinson's disease. (leeds.ac.uk)
A short region of the alpha-synuclein protein, known as NAC, was assumed to be key to Parkinson's disease, as it is particularly aggregation-prone. (leeds.ac.uk)

They share a common structural motif of helical fibrils formed by three protein subunits. (axonmedchem.com)

Her achievements have involved the innovative application of biophysical techniques to protein folding problems. (wikipedia.org)
This polymorphism indicates that the entire aggregation process, including oligomerization, should be heterogeneous, which complicates biophysical and biochemical characterizations of Aβ. (biorxiv.org)
Our laboratory uses a combination of biophysical, structural and computational techniques to understand these features. (berkeley.edu)
We have taken a proteomic and biophysical approach to understand how a protein fine-tunes its landscape to control this feature. (berkeley.edu)
Our research relies on a combination of multiple biochemical and biophysical techniques including recombinant protein expression and purification, NMR, cryo-EM and SAXS. (lu.se)

In 2021, an advance in biomolecular design was the creation of new proteins that were shown in the lab to spontaneously fold into their intended structures and embed into lipid membranes as reported in Science with lead author Anastassia Vorobieva. (wikipedia.org)
Most proteins must fold into defined three-dimensional structures to gain functional activity. (nature.com)
This results not only in different protein-protein interactions, but even proto-filaments with the same components but with significantly different structures (ultrastructural polymorphs). (technologynetworks.com)
Aβ forms amyloid fibrils, long fibers with parallel (or anti-parallel) β-sheet structures (cross-β structure). (biorxiv.org)
Proteins from thermophilic organisms must retain their native structures under extreme conditions, where their homologues from mesophilic organisms denature. (berkeley.edu)
These deposits often recruit various sugars and other components such as Serum Amyloid P component , resulting in complex, and sometimes heterogeneous structures. (wikidoc.org)
Moreover, they observed that the filaments have distinct structures depending on the protein mutation from which they originate. (sciencedaily.com)
We also cannot exclude the possibility that the structures of both proteins and polymers determine the balance between attractive and repulsive forces that drive protein-polymer interactions. (usf.edu)
Here we report crystal structures of variants of the cytotoxic oligomer-forming segment residues 28-38 of the ALS-linked protein, SOD1. (cornell.edu)

The encoded protein represents the A2 form, which is a monomeric protein with different biochemical properties from the A1 and A3 forms. (nih.gov)

Aggregation to form fibrils is also highly heterogeneous in terms of the number of strands in a fibril and the elongation speed and conformation of fibrils. (biorxiv.org)
In addition to the native conformation, a protein sequence populates small fluctuations around the native state, partially unfolded forms and even the globally unfolded conformation. (berkeley.edu)

Bruker's GHz-class NMR technology enables novel research in functional structural biology of proteins and protein complexes like intrinsically disordered proteins (IDPs). (bruker.com)
An intrinsically disordered protein (IDP) is a protein that is unable to fold into a stable or ordered three-dimensional structure. (bruker.com)
The biological importance of intrinsically disordered proteins (IDPs) has been discovered in recent years by sequence-specific assignments using NMR. (bruker.com)
Alpha-synuclein in solution is considered to be an intrinsically disordered protein, lacking a single stable 3D structure. (standardofcare.com)
The major constituent of LBs is aggregated α -synuclein ( α S), an intrinsically unfolded protein predominantly localized in the presynaptic regions of dopaminergic neurons. (hindawi.com)

Protein sequences hosted in bacterial cells that have shown resistance are harvested and their genes sequenced. (wikipedia.org)
Radford said that sequences will be uploaded to a database where advances in machine learning will eventually be able to identify patterns in protein sequences that can be scaled up for pharmaceutical production without needing any experiments. (wikipedia.org)
There are two broad classes of amyloid-forming polypeptide sequences. (wikidoc.org)

With their work, the researchers have confirmed the hypothesis that the granules of the brain pituitary gland are functional amyloids, which have an important physiological function in the secretion of hormones. (unibas.ch)

Radford's research investigates protein folding, protein aggregation and amyloid disease. (wikipedia.org)
A second research focus is on the folding of outer membrane proteins of Gram-negative organisms. (wikipedia.org)
Her early work in Oxford on hen lysozyme was the foundation for current views that proteins fold on complex multidimensional landscapes, commonly known as folding funnels. (wikipedia.org)
But in the cellular environment, newly synthesized proteins are at great risk of aberrant folding and aggregation, potentially forming toxic species. (nature.com)
Figure 1: Competing reactions of protein folding and aggregation. (nature.com)
Bartlett, A. I. & Radford, S. E. An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms. (nature.com)
Skach, W. R. Cellular mechanisms of membrane protein folding. (nature.com)
A large scale test of computational protein design: folding and stability of nine completely redesigned globular proteins. (nih.gov)
There are over 40 identified human disorders that involve certain proteins folding incorrectly, accumulating in the body causing damage to cells and organs and causing disease. (londonmet.ac.uk)
Understanding the sequence determinants of the energy landscape is therefore fundamental to the biological process that proteins carry out as well as protein folding itself. (berkeley.edu)
This hypothesis unites a lot of work in the field of and has also provided insight and experimental tests for current theoretical work on protein folding. (berkeley.edu)
We have previously shown that increasing the hydrophobicity of PEG by adding a methyl group to every other monomer unit allowed the resulting polymer to alter protein folding and inhibit protein aggregation to amyloid fibrils. (usf.edu)
Efficient refolding of aggregation prone Citrate Synthase by polyol osmolytes: How well are protein folding and stability aspects coupled? (jnu.ac.in)
Chemical chaperone mediated protein folding: Stabilization of P22 tailspike folding intermediates by glycerol. (jnu.ac.in)

We conclude that trapping amyloid precursor states in solution is a promising approach for understanding p53 aggregation in cancer. (bvsalud.org)

Alzheimer Disease Alzheimer disease causes progressive cognitive deterioration and is characterized by beta-amyloid deposits and neurofibrillary tangles in the cerebral cortex and subcortical gray matter. (msdmanuals.com)

The classical, histopathological definition of amyloid is an extracellular , proteinaceous deposit exhibiting cross-beta structure. (wikidoc.org)
For cell-cell adhesion, β-catenin binds the cytoplasmic domain of cadherin adhesion receptors along with the actin binding protein, α-catenin, to bridge the extracellular adhesive activity of cadherins with the underlying actin cytoskeleton. (axonmedchem.com)

In 2016, Radford received an Investigator Award in Science for Protein-protein interactions in the early stages of amyloid assembly mechanisms. (wikipedia.org)
The study of the underlying mechanisms of tau aggregation requires inspection of the assembly process in a controlled environment. (technologynetworks.com)
We have found that although protein stability can be altered by single amino acid substitution, evolution for optimal function requires more subtle and delocalized mechanisms.Recent results implicate structure in the unfolded state as playing an important and novel role for the thermostability of these proteins. (berkeley.edu)

Some natural phenolic compounds extracted from plants exhibit certain anti-amyloid activity in vitro and in vivo ( Stefani and Rigacci, 2013 ). (elifesciences.org)
As these observations cannot be practically made in vivo , recombinantly expressed protein fragments are often used for in vitro model systems of protein aggregation. (technologynetworks.com)
Zusätzlich können die Phosphorylierungnachahmer (S129E und S129D) den Effekt von Phosphorylierung auf die strukturellen und Aggregations-Eigenschaften von S in vitro nicht reproduzieren. (uni-goettingen.de)
Zn(2+) enhances TTR aggregation in vitro, and is a component of ex vivo TTR amyloid fibrils. (rcsb.org)
Spectroscopic characterization of diverse amyloid fibrils in-vitro by the fluorescent dye Nile red. (jnu.ac.in)

The build-up of these TTR amyloid fibrils in the heart leads to ATTR-CM. There is currently no cure for ATTR-CM. Alhamadsheh's team (in collaboration with Stanford University) developed a small molecule, called AG10, that stabilises TTR against amyloidoisis. (researchoutreach.org)

The amino acid changes could alter the protein charge and stability, inducing distinct physiological functions. (dovepress.com)

CsgE is a periplasmic accessory protein that plays a crucial role in curli biogenesis. (wustl.edu)
The Enterobacteriaceae in the human gut, can create curli, which are functional amyloid proteins. (standardofcare.com)

The alpha-synuclein protein is made of 140 amino acids. (standardofcare.com)

How and which interactions between two types of protein could be involved in protein aggregation is not completely understood. (neurodegenerationresearch.eu)
Moreover, it is still not clear which domains in these proteins can interact and what effects result from these interactions. (neurodegenerationresearch.eu)
Moreover, iron interactions with N-terminally acetylated α S, the physiologically relevant form of the human protein, will be addressed to shed light on the current understanding of protein dynamics and the physiological environment in the disease state. (hindawi.com)
He heads a multi-disciplinary team working in the field of protein-protein interactions. (researchoutreach.org)

These proteins may accumulate locally, causing relatively few symptoms, or widely, involving multiple organs and causing severe multiorgan failure. (msdmanuals.com)

Fig. 4: The selected cyclic pentapeptides AβC5-34 and AβC5-116 inhibit Aβ-induced aggregation and cytotoxicity in vivo. (nature.com)

As a continuation of this work, we analyzed here the effects of this substitution on the structural properties of proteins capable of adopting multiple conformations (folded, and different partially folded states, e.g. a molten globule-like intermediate) at mild denaturing conditions. (usf.edu)
We were especially interested in the relative sensitivity of partially folded (e.g. molten globule) conformations of these proteins to the presence of polymers as these conformations are often the most sensitive to the environment. (usf.edu)

ins in amyloid fibrils are still only understood in outline.Here in Chapter 3, it is demonstrated, by a combination of solution-state and solid-state NMR spectroscopy, that the structure of amyloid fibrils of á-synuclein (aS) is directly correlated to the conformational properties of the unfolded state and monomeric state of misfolding proteins. (uni-goettingen.de)
Hydrogen-deuterium exchange mapping of Abeta 1-40 amyloid fibril secondary structure using nuclear magnetic resonance spectroscopy. (jnu.ac.in)

The results confirm that, as for globular proteins, highly specific polypeptide sequential traits govern the assembly pathway, final fine structure, and cytotoxic properties of amyloid conformations. (ibecbarcelona.eu)

Fluorescence experiments revealed conformational changes of the single Trp and Tyr residues before p53 unfolding and the presence of MG conformers, some of which were highly prone to aggregation. (bvsalud.org)

Experimental and theoretical analyses led to the identification of two key intermediates en route to DHPs and the explanation of the observed regioisomeric ratios. (ac.rs)

In 2020, a collaboration between scientists at the University of Leeds and AstraZeneca led to the development of a technique that, "allows fragments of antibodies to be screened for susceptibility to aggregation caused by structure disruption much earlier in the drug discovery process. (wikipedia.org)

While stability of the monomer of TTR decreases in the presence of Zn(2+), which is consistent with the tertiary structural perturbation provoked by Zn(2+) binding, tetramer stability is only marginally affected by Zn(2+). (rcsb.org)

Proteins undergo an incredible transformation from one-dimensional sequence information into complex three-dimensional shapes that carry out intricate cellular functions. (berkeley.edu)

These fibril proteins are deposited into various organs and tissues, preferentially the nervous system and cardiac tissue, resulting in their inherent dysfunction. (medscape.com)
The ECM provides much of the structural support available to parenchymal cells in tissues. (axonmedchem.com)
A tetrameric form of α S has also been identified in human tissues that has been postulated as the inactive storage form of this structurally dynamic protein due to its aggregation resistance [ 6 , 7 ]. (hindawi.com)

In addition to the fibrillar amyloid protein, the deposits also contain serum amyloid P component and glycosaminoglycans. (msdmanuals.com)
Amyloid deposits stain pink with hematoxylin and eosin, contain carbohydrate constituents that stain with periodic acid-Schiff dye or with Alcian blue, but most characteristically have apple-green birefringence under polarized light microscopy after Congo red staining. (msdmanuals.com)
The amyloid deposits themselves are metabolically inert but interfere physically with organ structure and function. (msdmanuals.com)

Aβ interacts with many proteins either specifically or non-specifically as a monomer and various oligomeric forms 8 . (biorxiv.org)

evidence of a direct role of HSV-1 in the process of amyloid nucleation and subsequent fibril growth is currently lacking" (p. 7, 2nd last para). (alzforum.org)
In this work, we probe the determinants of secondary nucleation by studying its influence in different temperatures and pH and we confirm that it remains an important factor in aggregation in human cerebrospinal fluid. (lu.se)

Apolipoprotein E (APOE) is a lipid-transport protein abundantly expressed in most neurons in the central nervous system. (dovepress.com)

This heterogeneity in all stages of aggregation explains diverse and sometimes irreproducible results of experimental studies of amyloid-β. (biorxiv.org)
A more fundamental reason for the difficulty may be the heterogeneity of the aggregation process. (biorxiv.org)

though only certain proteins, for example, amyloids and silks, do so under normal physiological conditions. (ox.ac.uk)

The A2 form of pancreatic procarboxypeptidase acts on aromatic C-terminal residues and is a secreted protein. (nih.gov)
Vasopressin is stored in the cell in the form of amyloid-like granules. (unibas.ch)
The mutant form of tumor suppressor protein, p53, has recently been shown to exhibit prion-like properties. (bvsalud.org)
The misfolding and aggregation of this enzyme is associated with the familial form of the fatal neurodegenerative disease amyotrophic lateral sclerosis. (lu.se)

Anatomy21

Organisms15

Diseases18

Chemicals and Drugs95

Analytical, Diagnostic and Therapeutic Techniques and Equipment39

Psychiatry and Psychology2

Phenomena and Processes71

Disciplines and Occupations4

Technology, Industry, Agriculture3

Information Science5

Health Care2

Oligomers18

Aggregates21

Alzheimer's17

Peptides3

Fibril formation8

Known as amyloid fibrils2

Peptide8

Deposition11

Islet2

Insoluble6

Diseases13

Toxicity of amyloid fibrils1

Pathways5

Amyloidosis7

Amyloidogenic3

20221

Different amyloid1

Mechanism10

Molecular14

Formation11

Parkinson's5

Fibrils formed1

Biophysical5

Structures9

Biochemical1

Conformation2

Intrinsically5

Sequences3

Functional amyloids1

Folding14

Precursor1

Beta-amyloid1

Extracellular2

Mechanisms3

Vitro5

ATTR1

Amino acid1

Curli2

Alpha-synuclein protein1

Interactions4

Accumulate1

Inhibit1

Molten globule2

Spectroscopy2

Globular proteins1

Prone1

Intermediates1

20201

Stability1

Undergo1

Tissues3

Deposits3

Oligomeric1

Nucleation2

Neurons1

Heterogeneity2

Certain proteins1

Form4