Aggregation protein conformation. Medical search. Frequent questions

The development of computational tools opened a new avenue to rationalize this phenomenon, enabling prediction of the aggregation propensity of individual proteins as well as proteome-wide analysis. (uab.cat)
While the binding did not to appear to affect protein conformations in solution, extended incubation of the amyloidogenic variants in the presence of different ECM components resulted in different aggregation propensity and aggregation patterns. (lu.se)
Recently, we have developed massively parallel approaches based on Deep Mutational Scanning (DMS) to quantify the toxicity or the aggregation propensity of hundreds of thousands of protein sequences in vivo . (ibecbarcelona.eu)
By employing a biomimetic approach, we generated an extensive panel of optimized sequences of IAPP, which could drastically reduce aggregation propensity. (phoenixpeptide.com)
A structural and cellular characterization analysis was performed on the C-terminal domain with the highest aggregation propensity. (phoenixpeptide.com)

In this case, a native conformation does not have to be at the lowest energy trough of the diagram as shown, it must simply exist in its natural and kinetically accessible conformation in biological systems. (wikipedia.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)
IbpA and ibpB proteins are chaperones that are responsible for refolding aggregated bodies and inclusion bodies into their native conformation. (igem.org)

The formation of amyloid fibrils, insoluble aggregates of hydrophobic protein can lead to a myriad of diseases including Parkinson's and Alzheimer's disease. (wikipedia.org)
Fluorescence microscopy and filter trap assay are conventional methods to study protein aggregates, but cannot be used to analyze the presence and levels of post-translational modifications of aggregated Htt such as ubiquitination. (nih.gov)
Misfolded proteins are sticky and tend to form intracellular aggregates underpinning age-related deterioration and diseases including cancer and neurodegeneration. (cam.ac.uk)
[10] Furthermore, evidence has emerged that small, non-fibrillar protein aggregates known as oligomers are toxic to the cells of an affected organ, and that amyloidogenic proteins in their fibrillar form may be relatively benign. (wikipedia.org)
Lessons learned in this disease could help foster understanding of how these types of diseases develop, and what role the protein aggregates play. (neurodegenerationresearch.eu)
In Parkinson's disease, the protein alpha-synuclein aggregates within neurons of patients and appears to propagate across interconnected areas of the brain. (neurodegenerationresearch.eu)
Instead, damaged or incorrectly synthesized proteins must be rapidly and efficiently destroyed lest they form toxic aggregates. (stanford.edu)

The reason why Peter Lansbury and others used the term 'natively unfolded' for a-synuclein and other proteins, especially peptides, is that they do not exist, to a significant degree, in the same kind of stable structure that larger native proteins like myoglobin do. (alzforum.org)
Atomistic simulations of amyloidogenic peptides and their aggregation. (strodel.de)

The pathogenic mutation T182A converts the prion protein into a molten globule-like conformation whose misfolding to oligomers but not to fibrils is drastically accelerated. (ncbs.res.in)
This observation suggests that oligomers are unlikely to play a productive role on the direct pathway of aggregation from monomer to fibrils. (ncbs.res.in)
Apolipoprotein A-I (ApoA-I) amyloidosis is a rare protein misfolding disease where fibrils of the N-terminal domain of the protein accumulate in several organs, leading to their failure. (lu.se)
The aggregation of proteins into insoluble amyloid fibrils is a key process in the pathogenesis of a number of neurodegenerative conditions, such as Parkinson's disease or Amyotrophic Lateral Sclerosis. (ibecbarcelona.eu)
[9] However, some proteinaceous lesions lack birefringence and contain few or no classical amyloid fibrils, such as the diffuse deposits of amyloid beta (Aβ) protein in the brains of people with Alzheimer's. (wikipedia.org)
Although the accumulation of amyloidogenic proteins in neuroinflammatory conditions is generally considered pathologic, in a murine model of multiple sclerosis, amyloid-forming fibrils, comprised of hexapeptides, are anti-inflammatory. (phoenixpeptide.com)
In the absence of SDS, κ-casein aggregation proceeded to typical amyloid fibrils, whereas, in the presence of SDS, the aggregation yielded large oligomers. (ias.ac.in)

Protein conformation diseases, including polyglutamine (polyQ) diseases, result from the accumulation and aggregation of misfolded proteins. (nih.gov)
It ensures proper protein folding and prevents the accumulation of misfolded proteins, thereby safeguarding cellular health. (umu.se)
Although ApoA-I amyloidosis is systemic, the different amyloidogenic variants show a preferential tissue accumulation that appears to correlate with the location of the mutation in the protein sequence and with the local extracellular microenvironment. (lu.se)
Data indicated that ApoA-I variants exerted a cytotoxic effect in a time and cell-type-specific manner that seems to be due to protein accumulation in lysosomes. (lu.se)
We also observed a dose-dependent accumulation of polyubiquitinated proteins and loss of proteasomal function in CuO NP-exposed cells, and we could demonstrate misfolding and mitochondrial translocation of superoxide dismutase 1 (SOD1), a Cu/Zn-dependent enzyme that plays a pivotal role in the defense against oxidative stress. (biomedcentral.com)
Reduced nuclear localization of the transcription factor Msn2 and lower glycogen accumulation indicated higher protein kinase A (cAMP-dependent protein kinase, PKA) activity in many light-sensitive gene deletion strains. (biomedcentral.com)

Gurry T., Stu ltz CM. Intrinsically Disordered Proteins: Where Computation Meets Experiment. (mit.edu)
in Intrinsically Disordered Proteins . (mit.edu)
Stultz CM. Constructing Ensembles for Intrinsically Disordered Proteins. (mit.edu)
Huang A., Stultz CM. Modeling Intrinsically Disordered Proteins with Bayesian Statistics. (mit.edu)
Moreover, it only treats about half of the human proteome, as the remaining proteins are intrinsically disordered or contain disordered regions. (inra.fr)
However these intrinsically disordered proteins (IDPs) also systematically differ in amino acid composition and uniquely often become folded upon binding to an interaction partner. (inra.fr)
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)
Intrinsically disordered proteins (IDPs) belong to an important class of proteins that do not fold up spontaneously. (ias.ac.in)

The gene associated with Huntington's makes a protein that has a repetitive sequence called polyglutamine. (neurodegenerationresearch.eu)
To address this, we examined the role of natural variation in defining the susceptibility of genetically diverse individuals to protein aggregation and toxicity, using the Caenorhabditis elegans polyglutamine model. (biomedcentral.com)
For example in HD, the age of neurological onset is strongly associated with the length of polyglutamine (polyQ) expansion in huntingtin protein. (biomedcentral.com)

The polypeptide interacts with water, thus placing thermodynamic pressures on these regions which then aggregate or "collapse" into a tertiary conformation with a hydrophobic core. (wikipedia.org)
This approach is specifically described for use with mammalian cell culture and is suitable to study other disease-related proteins prone to aggregate. (nih.gov)
For example, cystic fibrosis is caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) protein, [3] and in amyotrophic lateral sclerosis / frontotemporal lobar degeneration (FTLD), certain gene-regulating proteins inappropriately aggregate in the cytoplasm, and thus are unable to perform their normal tasks within the nucleus. (wikipedia.org)
In Huntington's and several other progressive brain diseases, certain proteins aggregate to form plaques or deposits in the brain, said senior investigator Patrick C.A. van der Wel, Ph.D., assistant professor of structural biology at Pitt School of Medicine. (neurodegenerationresearch.eu)
These factors preclude solving IDP structures by current machine-learning methods like AlphaFold, which also cannot solve the protein aggregation problem, since this meta-folding process can give rise to different aggregate sizes and structures. (inra.fr)
This can cause the proteins to misfold and form aggregate bodies. (igem.org)
Due to lack of optimal folding conditions proteins can form aggregate bodies and cause activation of heat shock systems, chaperone systems and proteolytic pathways which are involved in either refolding the proteins into their native form or degrading the aggregate bodies. (igem.org)

Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases. (nih.gov)
Huntington's disease (HD) is one of nine diseases caused by an expanded polyQ repeat within the affected protein and is hallmarked by intracellular inclusion bodies composed of aggregated N-terminal huntingtin (Htt) fragments and other sequestered proteins. (nih.gov)
Delineation of the effects of pathogenic mutations linked with familial prion diseases, on the structure and misfolding of prion protein (PrP), will be useful in understanding the molecular mechanism of PrP misfolding. (ncbs.res.in)
They are also prone to aggregation, a phenomena which has been implicated for many diseases (the so-called misfolding and amyloid diseases). (berkeley.edu)
proteinopathic adj ), or proteopathy , protein conformational disorder , or protein misfolding disease , is a class of diseases in which certain proteins become structurally abnormal, and thereby disrupt the function of cells , tissues and organs of the body. (wikipedia.org)
He added Huntington's is one of many neurodegenerative diseases in which unusual protein deposition occurs in the brain, suggesting similar biochemical mechanisms may be involved. (neurodegenerationresearch.eu)
Monogenic gain-of-function protein aggregation diseases, including Huntington's disease, exhibit substantial variability in age of onset, penetrance, and clinical symptoms, even between individuals with similar or identical mutations. (biomedcentral.com)
Resistance to protein aggregation and the ability to restrict its associated cellular dysfunction are independently controlled by the natural variation in genetic background, revealing important new considerations in the search for targets for therapeutic intervention in conformational diseases. (biomedcentral.com)
Prion diseases are a group of degenerative illnesses of the brain caused when a molecule called the prion protein (PrP for short) adopts the wrong shape. (elifesciences.org)
These diseases are caused by refolding of the cellular prion protein (PrP C ) into an infectious isoform (PrP Sc ) that catalytically templates its abnormal conformation onto additional molecules of PrP C ( Prusiner, 1998 ). (elifesciences.org)
Mounting evidence suggests that the genetic disorders/mutation and diseases change not only the protein expression patterns but also membranes themselves. (lu.se)

Hydrophobic collapse is one of the main events necessary for reaching a protein's stable and functional conformation. (wikipedia.org)
With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation 11 , suggesting important functional correlations between repeat length and pathology. (nature.com)
By using ensemble FRET and Sp-FRET (Single Pair-Fluorescence Resonance Energy Transfer), we have probed the conformation of the model substrate DM-MBP (Double Mutant Maltose Binding Protein) during different stages of the functional cycle of GroEL. (uni-muenchen.de)
In this review, we assess the potential role of putative gut microbiota products in the etiopathogeny of Parkinson's disease, with a special emphasis on functional bacterial amyloid proteins, bacterial biosurfactants, endotoxins and short-chain fatty acids. (techscience.com)
Our work aims at systematically deciphering the sequence-dependencies of the process of aggregation in both functional and pathological contexts. (ibecbarcelona.eu)
Our goal is to elucidate the functional networks that coordinate protein synthesis and quality control in the early secretory pathway. (stanford.edu)
Lastly, since Mst77F arises when the genome is still in histone-based configuration my aim was to investigate binding-, structural- and functional effects also in the context of recombinant chromatin.The present work presents the first comprehensive in vitro study on a DNA architecture protein presumably involved in DNA condensation during postmeiotic spermatid maturation in Drosophila. (uni-goettingen.de)

Allergenicity of food proteins has been correlated to their structural conformation and their resistance to proteolysis. (cea.fr)
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations. (bvsalud.org)

In this model, we do not consider the interactions of the peptide backbone as this maintains its stability in non-polar and polar environments as long as there is sufficient hydrogen bonding within the backbone, thus we will only consider the thermodynamic contributions of the side chains to protein stability. (wikipedia.org)
Ubiquitination of proteins can be a signal for degradation and intracellular localization, but also affects protein activity and protein-protein interactions. (nih.gov)
Specifically, aggregation was found to be associated with increased cell fitness in the case of TDP-43 mutations, as it protects the host from aberrant interactions. (frontiersin.org)
Any situation, such as mutations or anomalous expression, could result in disruption of these beneficial interactions with consequent aggregation and depletion of normal function. (frontiersin.org)
GroEL encapsulates the substrate into the central cavity where folding occurs unimpaired by aggregation and unwanted inter-molecular interactions. (uni-muenchen.de)
We are also interested in developing similar high-throughput strategies to measure in vivo the effect of mutations on the physical state the proteins acquire upon mutation (diffuse, liquid de-mixed, insoluble) and to study the interactions between mutations to report on the conformations proteins adopt as they self-assemble. (ibecbarcelona.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)
In this conformation protein-protein interactions via the N-terminus are rare. (uni-goettingen.de)
All or other nearby charged groups, the pKa shift of a buried pH-dependent properties of proteins are ultimately governed residue is dominated by the large electrostatic self-energy by the electrostatic interactions of ionizable side chains. (lu.se)
2004). The effect of electrostatic interactions is usually polarization effects in the protein are subsumed in an quantified in terms of the shift, DpKa, of the pKa value of an apparent dielectric constant, eP. (lu.se)
The platelet GP IIb/IIIa complex mediates platelet-to-platelet interactions (platelet aggregation). (medscape.com)

Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer's disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. (nih.gov)
Hydrogen-deuterium exchange studies in conjunction with mass spectrometry indicate that the T182A mutation disrupts the core of the protein, thereby increasing overall structural dynamics. (ncbs.res.in)
For instance, many proteins share the same native structure yet their cellular dynamics and function, in other words their energy landscapes, are different. (berkeley.edu)
On the combined power of simulation and experiment to model protein structure, dynamics, function and assembly mechanisms. (strodel.de)
Protein Structure and Dynamics of Bacillus Subtilis Lipase LipA Fused to the Ligand-Binding Domain of Sensor Histidine Kinase CitA. (strodel.de)
An alternative computational method is provided by molecular dynamics simulations that already successfully explored the energy landscapes of IDP conformational switching and protein aggregation in multiple cases. (inra.fr)
In this review, I discuss the characteristics of these multifunneled energy landscapes in detail, illustrated by molecular dynamics simulations that elucidated the underlying conformational transitions and aggregation processes. (inra.fr)
While many studies have been focused on the membrane structure, the dynamics of such systems are crucial for the function of the membrane including membrane bound proteins. (lu.se)

We found that aggregation differentiates the effects of mutations in the two different cellular contexts. (frontiersin.org)
By contrast, in the case of TEM-1 beta-lactamase mutations, aggregation is linked to a decreased cell fitness due to inactivation of protein function. (frontiersin.org)
Evidence that the folding pathway inside the cage differs from that of spontaneous folding was obtained by observing the effect of external perturbations (e.g. mutations in substrate protein and use of different solvent conditions) on the rate of spontaneous and GroEL assisted folding reactions. (uni-muenchen.de)
Our lab aims at understanding how genetic changes between individuals can or cannot result in disease by quantifying the impact mutations have on protein aggregation and toxicity. (ibecbarcelona.eu)
We believe that by portraying the full landscape of the effects of mutations in a specific protein domain we can reach a more systematic and comprehensive understanding of the determinants of amyloid formation and toxicity. (ibecbarcelona.eu)
Proteins can also misfold due to mutations that occur in the coding region of the protein that can alter the amino acid sequence and thereby interrupting the native structure of the protein, causing it to misfold and be dysfunctional. (igem.org)
The Abeta plaques are a pathological hallmark of Alzheimer's disease, Abeta is the first biomarker that is altered, heritable forms of Alzheimer's rely on mutations in the Abeta protein* or enzymes involved in its production, and a mutation that reduces Abeta production protects against AD. (lu.se)
We then looked in mice with AD mutations where we also had accelerated the Abeta aggregation and found lots of aggregated Abeta inside the neurons at the first time points. (lu.se)

Hydrophobic collapse is a proposed process for the production of the 3-D conformation adopted by polypeptides and other molecules in polar solvents. (wikipedia.org)
For example, proteins that are normally unfolded or relatively unstable as monomers (that is, as single, unbound protein molecules) are more likely to misfold into an abnormal conformation. (wikipedia.org)
Antibodies are small protein molecules that are naturally expressed by the immune system of the body in response to the entry of a foreign molecule (antigen) and help in neutralizing it. (technologynetworks.com)
Within their conformation, prion strains encipher the information that directs the templated misfolding and aggregation of PrP C molecules into additional prions ( 1 ). (cdc.gov)

See also David Thirumalai's Emerging Ideas on the Molecular Basis of Protein and Peptide Aggregation ' (.pdf). (alzforum.org)

Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein 1 . (nature.com)
Using complementary approaches, i.e. controlled enzymatic hydrolysis and production of recombinant fusion proteins, we demonstrated that, for these patients, the allergenicity of the caprine β-casein could be abolished by substituting five amino acids residues. (cea.fr)
Isotope-edited FTIR in H2O: Determination of the conformation of specific residues in. (mtsu.edu)

Recent findings by scientists reveal that aggregation, spreading and pathology caused by alpha-synuclein do not necessarily involve prion-like seeding. (neurodegenerationresearch.eu)
Instead, they could be triggered by enhanced alpha-synuclein expression and trans-neuronal passage of monomeric and oligomeric forms of the protein. (neurodegenerationresearch.eu)
Our data also reveal that spreading and pathology can be triggered by simple overexpression of the protein and are mediated, at least initially, by monomeric and/or oligomeric alpha-synuclein. (neurodegenerationresearch.eu)
Although both of alpha-synuclein119 and alpha-synuclein133 showed a high cytotoxicity, alpha-synuclein133 showed a similar aggregation with full-length alpha-synuclein and no acceleration effect. (biomedcentral.com)

We found that aggregation is a transgressive trait, and does not always correlate with measures of toxicity, such as early onset of muscle dysfunction, egg-laying deficits, or reduced lifespan. (biomedcentral.com)

Just like all disordered protein regions, prion-like domains are particularly difficult to study in vitro . (ibecbarcelona.eu)
Although many truncated variants have been characterized, some of the truncated α-Syn variants which exist in both the normal and the pathogenic brain, such as α-Syn119 and α-Syn133, have not yet been investigated through in vitro aggregation and fibril formation studies. (biomedcentral.com)

Researchers have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder. (neurodegenerationresearch.eu)
For the first time, we were able to really look at the protein structure in the core of the deposits formed by the mutant protein that causes Huntington's. (neurodegenerationresearch.eu)

Globular proteins that are thought to fold by hydrophobic collapse are particularly amenable to complementary computational and experimental study using phi value analysis. (wikipedia.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)

Here, we set to clarify this complex matter and question of whether aggregation is an important constraint in protein evolution that can be the discriminant between beneficial and detrimental situations by considering two cases: we studied molecular evolution of proteins in an endogenous vs. exogenous host. (frontiersin.org)
Endogenous substances, usually proteins, that are involved in the blood coagulation process. (lookformedical.com)
Native membrane derived polymer-supported lipid bilayers (nSLBs) are poised to bridge the gap between live cell experiments and traditional model membrane architectures that by offering a combination of accessibility by surface sensitive analytical instrumentation and a composition which more closely resembles cellular membranes by displaying a diversity of endogenous membrane proteins, lipids, and carbohydrates. (lu.se)

Actual algorithms work on both protein sequences and structures, some of them accounting also for conformational fluctuations around the native state and the protein microenvironment. (uab.cat)
If two locally hydrophobic regions of two unrelated structures are left near each other in aqueous solution, aggregation will occur. (wikipedia.org)
To become biologically active, most proteins need to fold into precise three dimensional structures. (uni-muenchen.de)
Proteins from thermophilic organisms must retain their native structures under extreme conditions, where their homologues from mesophilic organisms denature. (berkeley.edu)
Instead, the energy landscapes of IDP conformational switching and protein aggregation feature a number of minima for different competing low-energy structures. (inra.fr)
However, spreading of aggregation towards highly condensed structures is mediated by cooperative protein multimerization. (uni-goettingen.de)

α-Synuclein (140 aa) is a natively unfolded protein that is enriched in the presynaptic terminal of the neurons in the brain. (biomedcentral.com)
By definition these proteins differ from natively folded proteins and do not adopt a properly folded structure in solution. (inra.fr)
Osmolytes enhance thermodynamic stability of proteins by stabilizing natively-folded protein conformation, thus preventing aggregation without perturbing other cellular processes. (apoe4.info)

Membrane proteins must be threaded co-translocationally into the lipid bilayer to become membrane-integrated, often with complex topologies and typically form hetero- or homo- oligomers. (stanford.edu)

Here, it has been shown that the pathogenic mutation T182A causes a drastic reduction in the apparent cooperativity and enthalpy of unfolding of the mouse prion protein (moPrP) under misfolding-prone conditions by converting the protein into a molten globule (MG)-like conformation. (ncbs.res.in)
CWD results from the conformational transformation of the host-encoded cellular prion protein (PrP C ) into protease-resistant, detergent-insoluble, β-sheet rich, amyloidogenic conformers, termed prions (PrP CWD ). (cdc.gov)
PrP C , the cellular isoform of the prion protein, serves to transduce the neurotoxic effects of PrP Sc , the infectious isoform, but how this occurs is mysterious. (elifesciences.org)

Indole excitation damages protein structure and integrity and may convert proteins into photosensitizers that produce reactive oxygen species (ROS). (biomedcentral.com)

This was confirmed by reduced proteolytic stability, impaired tetramer assembly or aggregation, increased hydrophobicity, and accelerated thermal unfolding--with particular impact on the regulatory domain--observed in most variants. (drugbank.com)

The majority of proteins function as monodispersed ordered species dissolved in intra- or extra-cellular aqueous fluids. (frontiersin.org)
The vast majority of proteins entering the secretory pathway are synthesized on ribosomes docked at ER translocons and are co-transationally translocated into the ER lumen. (stanford.edu)

We are particularly interested in amino acid sequences that can adopt different conformations and undergo a process of self-assembly which results in distinct physical states. (ibecbarcelona.eu)
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)
Three-dimensional modeling revealed the involvement of functionally relevant amino acid networks that may communicate misfolding throughout the protein. (drugbank.com)
Also Betton et al designed MalE31such that there are two amino acid changes in the protein and it misfolds. (igem.org)
The ionizable amino acid side chains of proteins are usually located at the surface. (lu.se)

Moreover, the C-terminal region regulates the amyloid aggregation and fibril formation of α-Syn. (biomedcentral.com)

HDX-MS measures changes in mass associated with the isotopic exchange between amide hydrogens of the protein backbone and its surrounding solvent. (evans-nguyen.org)

Molecular chaperones assist the folding of newly synthesized and denatured proteins in acquiring their native state in the crowded intracellular environment. (uni-muenchen.de)
Recently, it has become clear that proteins can also self-assemble into a more dynamic and reversible state through a process of liquid de-mixing which is thought to contribute to the organization of the intracellular space. (ibecbarcelona.eu)

Our use of different hydrogen exchange methods to study three different types of intermediates of E. coli ribonuclease H (the acid molten globule, the higher energy conformations of the native state and a kinetic folding intermediate) has been particularly powerful. (berkeley.edu)

In Drosophila Mst77F has been implicated in the DNA condensation process on the basis of immunocytology experiments and its distant sequence homology towards histone H1 family proteins and protamines. (uni-goettingen.de)

The c-type cytochrome (OmcB) and the multicopper protein (OmpB) required for Fe(III) oxide reduction by Geobacter sulfurreducens were predicted previously to be outer membrane proteins, but it is not clear whether they are positioned in a manner that permits the interaction with Fe(III). (shengsci.com)

Small heat shock proteins (sHsp) constitute an evolutionary conserved yet diverse family of chaperones acting as first line of defense against proteotoxic stress. (cam.ac.uk)
This class of proteins are called small heat shock proteins (sHsps). (igem.org)
In our cytoplasmic stress detector circuit, we decided to fuse two different promoter regions from two heat shock proteins, which are ibpAB and fxsA. (igem.org)

Proteins undergo an incredible transformation from one-dimensional sequence information into complex three-dimensional shapes that carry out intricate cellular functions. (berkeley.edu)
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)
In the 1990s, it was discovered that the patients have mutated proteins in which this sequence is too long, yet it has remained unclear how exactly this unusual mutation causes the protein to misbehave, clump together and cause the disease. (neurodegenerationresearch.eu)
For example: if a periplasmic protein lacked a signal sequence it will misfold in the cytoplasm because the conditions are different in the two cellular compartments. (igem.org)
The native E. coli protein MalE generally exported into the periplasmic space but this mutated protein does not get exported to the periplasmic space due to the signal sequence deletion. (igem.org)
To address this hypothesis I conducted bioinformatic analysis of the Mst77F protein sequence to identify a putative DNA interaction domain. (uni-goettingen.de)

[9] Subsequent research has shown that many different proteins can form amyloid, and that all amyloids show birefringence in cross- polarized light after staining with the dye Congo red , as well as a fibrillar ultrastructure when viewed with an electron microscope . (wikipedia.org)

Despite its deleterious impact on fitness, protein aggregation is a generic property of polypeptide chains, indissociable from protein structure and function. (uab.cat)
The driving force behind protein folding is not well understood, hydrophobic collapse is a theory, one of many, that is thought to influence how a nascent polypeptide will fold into its native state. (wikipedia.org)
The polypeptide will continue folding into lower energy states as long as these conformations are kinetically accessible. (wikipedia.org)
[13] [14] Because proteins share a common structural feature known as the polypeptide backbone, all proteins have the potential to misfold under some circumstances. (wikipedia.org)

However, the mechanisms utilized by proteins to avoid sampling the extraordinarily large amount of possible conformations during their folding process are just beginning to be understood. (uni-muenchen.de)
Overall, the exhaustive datasets we are generating will give mechanistic insights on the process of protein aggregation, while also reporting on specific conformations and mechanisms leading to cellular toxicity. (ibecbarcelona.eu)
A wide variety of photosynthetic and non-photosynthetic species sense and respond to light, having developed protective mechanisms to adapt to damaging effects on DNA and proteins. (biomedcentral.com)
Denatured collagen employed as a control exhibited higher energy absorption at its pI, suggesting different energy exchange mechanisms as a consequence of different aggregation routes. (biomedcentral.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)
Human and mouse prion proteins share a structural motif that regulates resistance to common chronic wasting disease (CWD) prion strains. (cdc.gov)

Partial hydrophobic collapse is an experimentally accepted model for the folding kinetics of many globular proteins, such as myoglobin, alpha-lactalbumin, barstar, and staphylococcal nuclease. (wikipedia.org)
In the absence of SDS, the aggregation kinetics of reduced and carboxymethylated (RCM) κ-casein followed a nucleation dependent polymerization model that comprises both lag- and assembly phases. (ias.ac.in)
On the contrary, in the presence of sub-micellar concentration of SDS, the aggregation kinetics did not exhibit a lag phase and appears to follow a non-nucleation pathway. (ias.ac.in)

Here, we analysed two deep mutational scanning experiments to investigate the role of protein aggregation in molecular evolution. (frontiersin.org)

Protein structure prediction using global optimization by basin-hopping. (strodel.de)
The protein folding problem was apparently solved recently by the advent of a deep learning method for protein structure prediction called AlphaFold. (inra.fr)

Using advanced nuclear magnetic resonance spectroscopy, we were able to provide an unprecedented view of the internal structure of the protein clumps that form in the disease, which we hope will one day lead to new therapies. (neurodegenerationresearch.eu)
Protein aggregation was determined by confocal microscopy using an aggresome-specific dye and protein misfolding was determined by circular dichroism (CD) spectroscopy. (biomedcentral.com)
We provide thorough characterization of the effect of pH, effect of salts and protein conformation on self-assembled collagen samples via several complementary biophysical techniques, including circular dichroism (CD), Fourier Transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), dynamic mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). (biomedcentral.com)

However, this program is not able to make predictions about the protein folding pathways. (inra.fr)

Fisher C., Ullman O., Stultz CM., Comparative Studies of Disordered Proteins with Similar Sequences: Application to AB40 and AB42. (mit.edu)
Optimized sequences with only one residue modification in the C-terminal core aggregation could diminish β-sheet formation and represent a novel strategy adaptable to other pharmacological targets. (phoenixpeptide.com)

Emphasis was made on the use of isothermal titration calorimetry (ITC) for the thermodynamic monitoring of fibrillogenesis stages of the protein. (biomedcentral.com)

how is it that GroEL is able to accelerate the rate of folding of certain proteins, and how do the conformational properties of the substrate change as it undergoes repeated cycling. (uni-muenchen.de)

Burger V., Arenas D., Stultz CM. A Structure-free Method for Quantifying Conformational Flexibility in proteins. (mit.edu)
The conformational flexibility of IDPs allows them to adopt a wide range of conformations depending upon their biochemical environment. (ias.ac.in)

Studying the ubiquitination pattern of aggregated Htt fragments offers an important possibility to understand Htt degradation and aggregation processes within the cell. (nih.gov)
Cellular proteostasis represents a finely tuned equilibrium between protein production, maintenance, and degradation that is crucial for cellular well-being. (umu.se)
Such non-native states on the energy landscape are thought to play a determining function in many cellular processes such as translocation, protein synthesis, degradation, signaling and allostery. (berkeley.edu)

Correct protein folding is integral to proper functionality within biological systems. (wikipedia.org)
Hydrophobic collapse can be visualized as part of the folding funnel model which leads a protein to its lowest kinetically accessible energy state. (wikipedia.org)
Imperiali B. Perturbing the folding energy landscape of the bacterial immunity protein Im7 by site-specific N-linked glycosylation. (mit.edu)
It has been well established that all the folding information is contained within the primary structure of a protein. (uni-muenchen.de)
Kinetic data obtained from ensemble FRET measurements suggest that the conformation of refolding intermediate is altered by the GroEL cavity, which leads to a folding pathway that is different from the spontaneous refolding pathway. (uni-muenchen.de)
In summary, this study revealed significant novel aspects of the GroEL folding mechanism and provided insights into the basis of rate acceleration of the substrate protein by the chaperonin. (uni-muenchen.de)
This work may thus contribute to advance our fundamental knowledge of the chaperonin system and the basic mechanism of protein folding. (uni-muenchen.de)
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)
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)
This machinery plays a pivotal role in cell survival under protein folding stress and in counteracting disease and age-associated cell toxicities. (cam.ac.uk)
In most, if not all proteinopathies, a change in the 3-dimensional folding conformation increases the tendency of a specific protein to bind to itself. (wikipedia.org)
Thus, PKU has evolved from a model of a genetic disease that leads to severe neurological impairment to a model of a treatable protein-folding disease with loss of function. (drugbank.com)
Protein Folding and Neurodegeneration: Biophysics to the Rescue? (alzforum.org)
This does not change our view of protein folding in the least. (alzforum.org)
These energy landscapes are very different from those of 'simple' protein folding, where one energy funnel leads to a unique protein structure. (inra.fr)
This highly complex 'protein biogenesis' process is assisted by a diverse network of folding catalysts and protein-modifying enzymes and is scrutinized by molecular chaperones and other 'quality control' factors which ensure that only correctly folded and assembled proteins exit the ER and proceed to distal compartments of the secretory pathway. (stanford.edu)

Knowing how a particular protein called dopamine transporter controls dopamine movement in and out of neurons is crucial to further understanding dopamine-related disorders. (neurodegenerationresearch.eu)
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)
So, we looked for aggregation there at very early time points before any plaques were formed outside the neurons. (lu.se)
Why do you think the aggregations inside the neurons disappeared when the plaques developed? (lu.se)
Initially, before plaques are formed, the neurons may just overproduce Abeta and this leads to aggregation inside the cells. (lu.se)
So, you think that aggregation of Abeta inside the neurons may be essential for Alzheimer's pathology, but how do prion-like properties come into the picture, as the title of your thesis indicates? (lu.se)

Introgression of polyQ40 into three wild genetic backgrounds uncovered wide variation in onset of aggregation and corresponding toxicity, as well as alteration in the cell-specific susceptibility to aggregation. (biomedcentral.com)

This maintains the stability of the structure within localized segments of the protein. (wikipedia.org)

Anatomy6

Organisms8

Diseases6

Chemicals and Drugs99

Analytical, Diagnostic and Therapeutic Techniques and Equipment54

Psychiatry and Psychology1

Phenomena and Processes85

Disciplines and Occupations7

Technology, Industry, Agriculture6

Information Science10

Health Care2

Propensity5

Native conformation3

Aggregates7

Peptides2

Fibrils7

Accumulation6

Intrinsically8

Polyglutamine3

Aggregate7

Diseases11

Functional7

Structural conformation2

Interactions11

Dynamics8

Mutations8

Molecules4

Peptide Aggregation1

Residues3

Alpha-synuclein4

Found that aggregation1

Vitro2

Huntington's2

Computational2

Endogenous3

Structures6

Natively3

Oligomers1

Prion protein3

Reactive oxygen1

Proteolytic1

Majority of proteins2

Amino5

Fibril1

Solvent1

Intracellular2

Molten globule1

Family Proteins1

Membrane Proteins1

Heat shock pr3

Sequence6

Amyloids1

Polypeptide4

Mechanisms4

Resistance2

Kinetics3

Deep mutational1

Prediction2

Spectroscopy3

Pathways1

Sequences2

Thermodynamic1

Certain proteins1

Conformational Flexibility2

Degradation3

Folding16

Neurons6

Susceptibility1

Stability1