• Highly conserved acidic residues found in the short periplasmic loop are not essential for CorA function or Mg 2+ selectivity but may be required for proper protein folding and stability. (tcdb.org)
  • These replacements also led to production of infective viruses that replaced the acidic residues introduced (E) by nonpolar amino acids, indicating that preservation of the hydrophobic interface is essential for virus replication. (asm.org)
  • Based on a predicted model of UMAMIT29, we propose that the substrate transporting cavity consists of 51 residues, of which four are highly conserved residues across all the analyzed homologs of UMAMIT29. (frontiersin.org)
  • We hypothesised that the transport cavity contains highly conserved residues that are key for the transport activity. (frontiersin.org)
  • The cytoplasmic neck of the pore is surrounded, on the outside of the funnel, by a ring of highly conserved positively charged residues. (tcdb.org)
  • Our chemical-shift based secondary structure analysis reveals the human DBNDD1 as an intrinsically disordered protein. (springer.com)
  • 2021 ), https://pfam.xfam.org/ ] predicts human DBNDD1 mainly as an intrinsically disordered protein (IDP) and also the recently released AlphaFold database (Jumper et al. (springer.com)
  • Human brain derived neurotrophic factor (BDNF) encodes a protein product consisting of a C-terminal mature domain (mature BDNF) and an N-terminal prodomain, which is an intrinsically disordered protein. (bvsalud.org)
  • Their amino acid sequences suggest that they are mainly cytosolic or nuclear proteins partly associating with membranes (Talbot et al. (springer.com)
  • 2009 ). The designated dysbindin paralogs show very limited sequence homology which raised the question whether DBNDD1 and DBNDD2 are dysbindin-like proteins or proteins that share a less conserved domain with DTNBP1 in the context of otherwise unrelated sequences (Ghiani and Dell'Angelica 2011 ). (springer.com)
  • We performed a Basic Local Alignment Search Tool (BLAST) analysis to identify regions of local similarity between the human DBNDD1 and protein sequences from other species (Fig. 1 ). (springer.com)
  • 2019 ) was used, https://www.ebi.ac.uk/Tools/msa/clustalo/ ] of human DBNDD1 and similar protein sequences found by a BLAST search in other selected species. (springer.com)
  • To test this, we aligned 97 protein sequences consisting of homologs of UMAMIT clade I from 27 plant species and created sequence logos containing the 51 residues identified in the structural analysis ( Supplementary Figure 1 ). (frontiersin.org)
  • The reports on base sequences of spider silk protein genes have gained importance as the mechanical properties of silk fibers have been revealed. (bioone.org)
  • This review aims to link recent molecular data, often translated into amino acid sequences and predicted three dimensional structural motifs, to known mechanical properties. (bioone.org)
  • Although protein structures have been solved by experiments at an increasing rate, a flood of new sequences have been determined even more rapidly due to the advance of sequencing technologies[ 6 , 7 ]. (biomedcentral.com)
  • At least four phylogenetically distinct groups of bacteria encode repeat proteins with the common ability to bind specific DNA sequences with a unique but conserved code. (uni-muenchen.de)
  • The channel is formed by an inner group of five helices and putatively gated by bulky hydrophobic residues. (tcdb.org)
  • A molecular model of the FMDV 3A protein, derived from the nuclear magnetic resonance (NMR) structure of the poliovirus 3A protein, predicted a hydrophobic interface spanning residues 25 to 44 as the main determinant for 3A dimerization. (asm.org)
  • Replacements L38E and L41E, involving charge acquisition at residues predicted to contribute to the hydrophobic interface, reduced the dimerization signal in the protein ligation assay and prevented the detection of dimer/multimer species in both transiently expressed 3A proteins and in synthetic peptides reproducing the N terminus of 3A. (asm.org)
  • Furthermore, GSOs protected cells against GLU-induced apoptosis by reducing the expression of the mitochondrial apoptosis-associated Bcl-2 family effector proteins and protected cells from GLU-induced oxidative damage by increasing the nuclear translocation of Nrf2 and HO-1 expression. (sdbonline.org)
  • RipTALs are effector proteins delivered during bacterial wilt disease caused by R. solanacearum strains. (uni-muenchen.de)
  • Deciphering protein–protein interactions. (crossref.org)
  • Protein-DNA interactions are involved in many fundamental biological processes essential for cellular function. (nature.com)
  • An analysis of the number of binding sites in the spatial context of the target site indicates that the interactions between binding sites next to each other are important for protein-DNA recognition and their binding ability. (nature.com)
  • Effective encoding of residue contact information is crucial for protein structure prediction since it has a unique role to capture long-range residue interactions compared to other commonly used scoring terms. (biomedcentral.com)
  • Among various structure-based terms, residue-residue contact potentials[ 21 - 23 ] are unique in that they capture long-range interactions in a protein structure[ 24 ]. (biomedcentral.com)
  • Replacements that favored (Q44R) or impaired (Q44D) the polar interactions predicted between residues Q44 and D32 did not abolish dimer formation of transiently expressed 3A, indicating that these interactions are not critical for 3A dimerization. (asm.org)
  • The p.Asn173His mutation affects a residue in the forkhead domain that is 100% conserved among vertebrate orthologs and is predicted to participate in protein-protein interactions. (molvis.org)
  • rium properties, completely determined by the interactions within crystal structures of 38 nonhomologous proteins, we find that it the system. (lu.se)
  • Most of the existing computational approaches employed only the sequence context of the target residue for its prediction. (nature.com)
  • In the present study, for each target residue, we applied both the spatial context and the sequence context to construct the feature space. (nature.com)
  • They are typically trained from a set of input features, which can be generally divided into three categories: protein sequence information, protein structure information and a combination of the two categories. (nature.com)
  • Protein sequence information mainly consists of amino acid residue composition, biochemical features of amino acid residues and evolutionary information in terms of position-specific scoring matrices (PSSM). (nature.com)
  • Yan and his coworkers 11 trained a Naïve Bayes classifier by using only sequence information, such as the identities of the target residue and its sequence neighboring residues. (nature.com)
  • Wang and his coworkers 12 investigated the discriminative power of three sequence features from protein sequence, including the side chain pKa value, the hydrophobicity index and the molecular mass of an amino acid. (nature.com)
  • As an outcome human DBNDD1 revealed a high sequence identity to dysbindin domain-containing proteins from other Hominidae (e.g. (springer.com)
  • Proteins with high sequence identity to human DBNDD1 can also be found in evolutionarily more distant species (e.g. (springer.com)
  • Finally, the signal sequence is cleaved and the pre-protein is either folded or trafficked onwards. (elifesciences.org)
  • Protein flexibility and rigidity predicted from sequence. (rostlab.org)
  • We used this analysis to develop a neural network-based method that predicts flexible-rigid residues from amino acid sequence. (rostlab.org)
  • The system uses both global and local information (i.e., features from the entire protein such as secondary structure composition, protein length, and fraction of surface residues, and features from a local window of sequence-consecutive residues). (rostlab.org)
  • The most important local feature was the evolutionary exchange profile reflecting sequence conservation in a family of related proteins. (rostlab.org)
  • Based on primary sequence comparisons, β subunits are predicted to be modular structures composed of five domains (A-E) that are related to the large family of membrane-associated guanylate kinase proteins. (jneurosci.org)
  • SH2 domains mediate intramolecular recognition and intermolecular protein-protein association almost invariably by binding to phosphorylated tyrosine (pY) residues in specific sequence contexts. (lu.se)
  • Here, using atomistic molecular dynamics simulation, we study the correlations between the RBD dynamics with physically distant residues in the spike protein, and provide a deeper understanding of their role in the infection, including the prediction of important mutations and of distant allosteric binding sites for therapeutics. (biorxiv.org)
  • We applied time-independent component analysis (tICA) and protein connectivity network model, on all-atom molecular dynamics trajectories, to identify key non-RBD residues, playing crucial role in the conformational transition facilitating spike-receptor binding and infection of human cell. (biorxiv.org)
  • A combination of molecular simulation with hydrogendeuterium-exchange mass spectrometry and electron paramagnetic resonance spectroscopy reveal an asymmetry across the membrane: ATP-induced conformational changes in the cytosolic cavity promote unfolded pre-protein structure, while the exterior cavity favours its formation. (elifesciences.org)
  • We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. (springer.com)
  • The tertiary structure of proteins provides crucial information for understanding molecular mechanisms of biological functions. (biomedcentral.com)
  • To identify catalytic residues, we generated a homology model of IroB from aligned structures of two similar C-glycosyltransferases as templates. (concordia.ca)
  • A loop containing possible catalytic residues (H65, H66, E67) was found at the predicted enterobactin-binding site. (concordia.ca)
  • They usually appear in multidomain proteins, together with catalytic domains, or other protein binding modules, such as Src homology 3 (SH3), phosphotyrosine binding (PTB) or pleckstrin homology (PH) domains. (lu.se)
  • The knowledge about DNA-binding residues, binding specificity and binding affinity helps to not only understand the recognition mechanism of protein-DNA complex, but also give clues for protein function annotation. (nature.com)
  • The yeast proteins appear to exhibit broad specificity transporting a wide range of di- and trivalent metal cations. (tcdb.org)
  • Each repeat binds a single DNA base, and specificity is determined by the amino acid residue at position 13 of each repeat. (uni-muenchen.de)
  • 2022 ) predicts human DBNDD1 - with a short stretch of helical propensity between residues L77 and S95 - entirely as an IDP. (springer.com)
  • Most members of the MIT family are between 300 and 400 amino acyl residues in length and possess two (or three) putative transmembrane α-helical spanners (TMSs). (tcdb.org)
  • Hydropathy analysis had predicted two transmembrane α-helical spanners (TMSs) in the C-terminal regions of these proteins. (tcdb.org)
  • As generation of site-specific PTMs in proteins is challenging, we used short synthetic peptides to quantify the effects on tubulin binding of three site-specific PTMs located within the PHF6∗ (paired helical filament [PHF] residues 275-280) and PHF6 (residues 306-311) hexapeptide motifs: K280 acetylation, Y310 phosphorylation, and K311 succinylation. (bvsalud.org)
  • The viral genome encodes four structural capsid proteins (VP1 to VP4) and seven nonstructural (NS) proteins, the leader Lb/ab protease, and proteins encoded in the P2 (2B and 2C) and P3 (3A, 3B, 3C, and 3D) regions ( 9 ). (asm.org)
  • The disulfide bond at 43-80 induces small structural rearrangements close to the site of the disulfide bond, associated with some local disorder: the crosslink appears to decrease the stability of the native form of the protein. (rcsb.org)
  • Superposition of our homology model onto the structure of a TDP-bound orthologue revealed residue W264 as a possible stabilizer of UDP-glucose. (concordia.ca)
  • The Src homology 2 (SH2) domains are about 100 residues in length with an average of 28% pairwise residue identity (Pfam code PF00017). (lu.se)
  • Mutation on these residues can lead to new strains of coronavirus with different degrees of infectivity and virulence. (biorxiv.org)
  • The most ubiquitous D614G mutation is predicted ab-initio from our model. (biorxiv.org)
  • Although SH2 domain containing proteins have been shown to have redundant functions in the cellular signaling networks, proteins with defective SH2 domains either have a crucial role during cell development process or they regulate multiple signaling cascades. (lu.se)
  • Bullock and Fersht 8 have shown that mutations of DNA-binding residues, such as those on the tumor repressor protein P53, may predispose individuals to cancer. (nature.com)
  • The goal of the present investigation is to examine the effects of missense mutations in the MERS-CoV S protein on protein stability and binding affinity with DPP4 to provide insight that is useful in developing vaccines to prevent coronavirus infection. (frontiersin.org)
  • We investigated the effects of MERS-CoV S protein viral mutations on protein stability and binding affinity. (frontiersin.org)
  • In addition, we studied all DPP4 mutations and found the functional substitution R336T weakens both DPP4 protein stability and S-DPP4 binding affinity. (frontiersin.org)
  • These findings provide further information on how mutations in coronavirus S proteins effect protein function. (frontiersin.org)
  • Significant research effort for drug design against COVID-19 is focused on the receptor binding domain of the spike protein, although this region is prone to mutations causing resistance against therapeutics. (biorxiv.org)
  • These residues can not only be targeted by broad spectrum antibodies and drugs, mutations in them can generate new strains of coronavirus resulting in future epidemic. (biorxiv.org)
  • 6 Significantly, the sites in S protein have been demonstrated to be vulnerable to acquire mutations. (biorxiv.org)
  • Truncating RAD21 variants are shown above, and missense mutations and in-frame deletions are shown below the protein representation. (springer.com)
  • By comparing differentially conserved residues within the predicted cavities between glucosinolate-transporting and non-glucosinolate-transporting UMAMITs, we identify 11 candidate residues. (frontiersin.org)
  • showing the cavities through the channel, with the protein in grey surface, the pre-protein pore constrictions in red (SecY) or purple (SecA) mesh, and the SecY plug in red helix. (elifesciences.org)
  • Based on our model, we proposed a substrate-transporting cavity of UMAMIT29 defined by helix I to IV and VI-IX and selected 51 residues as putative substrate binding sites based on solvent accessibility ( Figure 1 ). (frontiersin.org)
  • The yeast metal resistance proteins, which are 850-900 amino acyl residues in length, also exhibit two or three putative TMSs. (tcdb.org)
  • A key component in the virulence of MERS-CoV is the Spike (S) protein, which binds with the host membrane receptor dipeptidyl peptidase 4 (DPP4). (frontiersin.org)
  • Infection of human cells by the novel coronavirus (SARS-Cov-2) involves the attachment of the receptor binding domain (RBD) of the spike protein to the peripheral membrane ACE2 receptors. (biorxiv.org)
  • The bulk of protein secretion and membrane protein insertion is conducted by the ubiquitous Sec translocon. (elifesciences.org)
  • in poliovirus (PV), the interaction between the RNA replication complex and intracellular membranes appears to be accomplished by proteins 3A and 2C, which have membrane-binding properties ( 11 , 60 ). (asm.org)
  • Limited chemical shift dispersion represents a significant barrier to studying multistate equilibria of large membrane proteins by 19F NMR. (bvsalud.org)
  • A proper encoding of residue contact information is crucial for structure prediction because in principle, a full distance map or a residue contact map has sufficient information for reconstructing the tertiary structure of a protein[ 25 ]. (biomedcentral.com)
  • Zn2+ binds with higher affinity and more broadly impacts residues on the Met66 prodomain compared to the Val66 prodomain as shown by NMR and ITC. (bvsalud.org)
  • Thus, CNNM proteins, the vertebrate orthologues of CorB/C, also have Mg 2+ transport capacity. (tcdb.org)
  • 1 , 2 Largely expressed on the surface of SARS-CoV-2, the spike (S) protein plays a crucial role in binding to the host angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD) and facilitating viral entry, 3 , 4 which is therefore considered as one of the most preferred targets against SARS-CoV-2. (biorxiv.org)
  • NS proteins are involved in crucial aspects of the viral cycle and pathogenesis, such as rearrangements of intracellular membranes required for endomembrane recruitment and the lysis of host cells ( 1 , 12 , 14 , 18 , 73 ). (asm.org)
  • Our studies do not support the view that the conformation of the disulfide bond is crucial in determining the stability of the mutant proteins. (rcsb.org)
  • Eukaryotic expression vectors containing genes encoding plant proteins for killing of cancer cells. (weeksmd.com)
  • consequently, genes encoding some of these proteins are being used to design constructs for the inhibition of multiplying cancer cells. (weeksmd.com)
  • The genome-wide search for disease-causing variations in the SH2 domains revealed eight genes: Bruton tyrosine kinase (BTK), SH2 domain-containing protein 1A (SH2D1A), Ras GTPase activating protein (RasGAP), tyrosine protein kinase Zap-70, SHP-2, the p85α subunit of the PIP3 kinase (PI3-K), signal transducer and activator of transcription 1α/β (STAT1) and STAT5B. (lu.se)
  • Transport of proteins across membranes is a fundamental process, achieved in every cell by the 'Sec' translocon. (elifesciences.org)
  • The encapsulation and compartmentalisation of cells has necessitated the evolution of machineries that conduct proteins across membranes, including for protein secretion and organellar import. (elifesciences.org)
  • When each of the 11 residues of UMAMIT29 was individually mutated into the corresponding residue in UMAMIT32, five mutant variants (UMAMIT29#V27F, UMAMIT29#M86V, UMAMIT29#L109V, UMAMIT29#Q263S, and UMAMIT29#T267Y) reduced glucosinolate transport activity over 75% compared to wild-type UMAMIT29. (frontiersin.org)
  • Transport activity assays of mutant variants with a single point amino acid substitution in each site UMAMIT29 suggest that five of these residues are critical for glucosinolate transport. (frontiersin.org)
  • 5 , 7 - 9 More specifically, a study analyzing 10,022 SARS-CoV-2 genomes from 68 countries revealed 2969 different missense variants, with 427 variants in the S protein. (biorxiv.org)
  • Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. (springer.com)
  • Variants for which protein modelling is available, are marked in bold. (springer.com)
  • ClinVar variants which are reported in the ClinVar database and could be investigated for pathogeneity with protein modelling (see supplementary Table S6). (springer.com)
  • We generated IroB variants at positions 65-67, 264, and 304 and investigated variant protein conformations and enzymatic activities. (concordia.ca)
  • Therefore, a reliable identification of DNA-binding sites in DNA-binding protein is important for protein function annotation, in silico modeling of transcription regulation and site-directed mutagenesis. (nature.com)
  • The residue contact information can be incorporated in structure prediction in several different ways: It can be incorporated as statistical potentials or it can be also used as constraints in ab initio structure prediction. (biomedcentral.com)
  • To seek the most effective definition of residue contacts for template-based protein structure prediction, we evaluated 45 different contact definitions, varying bases of contacts and distance cutoffs, in terms of their ability to identify proteins of the same fold. (biomedcentral.com)
  • We compared the S protein structures of MERS-CoV, SARS-CoV, and SARS-CoV-2 viruses and identified the residues like C526, C383, and N468 located in equivalent positions of these viruses have effects on S protein structure. (frontiersin.org)
  • Crystal structures of the three mutant proteins have been solved. (rcsb.org)
  • In the very stable mutant 85-102, there is no significant difference between the mutant and wild-type structures: these data do not explain the large stability of this protein. (rcsb.org)
  • Repeat arrays of these proteins have been demonstrated or predicted to form almost identical tertiary structures: a right-handed super helix that wraps around the DNA double strand with the base specifying residue of each repeat positioned in the major groove next to its cognate target base. (uni-muenchen.de)
  • 2016). Here, we show that ATP enhances this process by modulating secondary structure formation within the translocating protein. (elifesciences.org)
  • Overexpression of the yeast proteins, Al R 1p and Mn R 2p, overcomes toxicity to aluminum and manganese, respectively. (tcdb.org)
  • Several experimental techniques have been proposed to identify the DNA-binding sites and investigate the interaction modes between proteins and DNAs. (nature.com)
  • B-values derived from experimental data are widely used to measure residue flexibility. (rostlab.org)
  • Foot-and-mouth disease virus (FMDV) nonstructural protein 3A plays important roles in virus replication, virulence, and host range. (asm.org)
  • This unity of terminology belies disunity in the lifestyles of these different bacteria, and the biological roles fulfilled by these proteins. (uni-muenchen.de)
  • In addition the TALEs and RipTALs may simply represent one face of the TALE-likes, a protein family mediating as yet unknown biological roles as bacterial DNA binding proteins. (uni-muenchen.de)
  • The dysbindin domain-containing protein 1 (DBNDD1) is a conserved protein among higher eukaryotes whose structure and function are poorly investigated so far. (springer.com)
  • This ability to exploit structure within a pre-protein is an unexplored area of protein transport, which may apply to other protein transporters, such as those of the endoplasmic reticulum and mitochondria. (elifesciences.org)
  • Intrinsically disordered regions (IDRs) lacking a fixed three-dimensional protein structure are widespread and play a central role in cell regulation. (iucr.org)
  • The crystal structure of the CorA homologue from Thermotoga maritima has been solved at 3.9 Å resolution for the full-length protein and at 1.85 Å resolution for the cytoplasmic domain ( Lunin et al . (tcdb.org)
  • In this series of papers, we examine the effects of introducing disulfide bonds on the properties, structure and thermodynamics of a small globular protein, barnase. (rcsb.org)
  • The primary data, structure factors of Bragg reflections, AMSDs can be predicted solely on the basis of packing density. (lu.se)
  • Yet, the local yield a set of mean atomic positions r 0 density, averaged over volume elements of 0.1-1 nm3, varies k r k that define the ``ground-state'' protein structure, or, if resolution permits, a small substantially within a protein (14, 17, 18). (lu.se)
  • The protein must then fold during or after the translocation process. (elifesciences.org)
  • Lower fold recognition accuracy was observed when inaccurate threading alignments were used to identify common residue contacts between protein pairs. (biomedcentral.com)
  • In the case of threading, alignment accuracy strongly influences the fraction of common contacts identified among proteins of the same fold, which eventually affects the fold recognition accuracy. (biomedcentral.com)
  • The largest deterioration of the fold recognition was observed for β-class proteins when the threading methods were used because the average alignment accuracy was worst for this fold class. (biomedcentral.com)
  • When results of fold recognition were examined for individual proteins, we found that the effective contact definition depends on the fold of the proteins. (biomedcentral.com)
  • Residue contacts defined by Cβ−Cβ distance of 7.0 Å work best overall among tested to identify proteins of the same fold. (biomedcentral.com)
  • We also found that effective contact definitions differ from fold to fold, suggesting that using different residue contact definition specific for each template will lead to improvement of the performance of threading. (biomedcentral.com)
  • All three proteins have essentially the same fold as wild-type, but with left-handed disulfide bonds, which have dihedral geometries that have not been observed in naturally occurring disulfides. (rcsb.org)
  • The S protein is responsible for helping the virus to gain entry to the cell contributing to the overall virulence of these β-CoVs. (frontiersin.org)
  • Here, we present the backbone and side chain nuclear magnetic resonance assignments for the human DBNDD1 protein. (springer.com)
  • proteins could carry out their biological functions. (lu.se)
  • In silico studies of protein flexibility have attempted to characterize and predict flexible regions based on simple principles. (rostlab.org)
  • larger amplitude are sampled and do not converge even in nano- about protein flexibility has come from x-ray crystallography, in the second-length simulations (8, 9). (lu.se)
  • In bacteria, this comprises SecY, SecE and usually SecG, with the protein-conducting pore running through the centre of SecY. (elifesciences.org)
  • This suggests that these residues are key for UMAMIT29-mediated glucosinolate transport activity and thus potential targets for blocking the transport of glucosinolates to the seeds. (frontiersin.org)
  • The CorA proteins of E. coli and S. typhimurium are each 316 amino acyl residues in length. (tcdb.org)
  • 18 The human immune system started generating antibodies specific to residues outside RBD even at the earlier stage of the pandemic. (biorxiv.org)
  • Site-specific mutagenesis studies of three conserved residues in TMS 3 suggest that they contribute to the Mg 2+ transport pathway. (tcdb.org)
  • Conversely, broad spectrum therapeutics like drugs and monoclonal antibodies can be generated targeting these key distant regions of the spike protein. (biorxiv.org)