Current Research in Structural Biology最新文献

{"title":"Error estimates in atom coordinates and B factors in macromolecular crystallography","authors":"John R. Helliwell","doi":"10.1016/j.crstbi.2023.100111","DOIUrl":"https://doi.org/10.1016/j.crstbi.2023.100111","url":null,"abstract":"<div><p>The overall diffraction precision index (DPI) of a biological macromolecule crystal structure was first described by Cruickshank in 1999. This topical review proceeds from this point and describes the subsequent elaboration of the index to individual atom coordinates. Additional developments were introduced by the availability of a webserver, which provides a transformed PDB entry with individual atom coordinate errors derived from applying the DPI method using the parameters provided by the authors and then subsequently added to the PDB file. This webserver has been extensively used and harnessed in describing non-covalent distance error estimates as well as assessing the significance, or otherwise, of atom movements in a variety of studies. The standard uncertainties on a biological macromolecule's atomic displacement parameters (the ‘B factors’) has been an entirely different challenge but is obviously important since the crystallographic community has developed the habit of quoting B factors to a false precision in papers. This can convey a false certainty in the dynamics of a structure. A method involving parallelisation of workflows for diffraction image data processing does however offer estimates of the precision of B factors.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"6 ","pages":"Article 100111"},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X2300017X/pdfft?md5=c61a8df4d4a4bf34ca647bfc7565dbdf&pid=1-s2.0-S2665928X2300017X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136694851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa","authors":"Killivalavan Asaithambi ,&nbsp;Iman Biswas ,&nbsp;Kaza Suguna","doi":"10.1016/j.crstbi.2022.05.003","DOIUrl":"10.1016/j.crstbi.2022.05.003","url":null,"abstract":"<div><p>Ddi1 is a multidomain protein that belongs to the ubiquitin receptor family of proteins. The Ddi1 proteins contain a highly conserved retroviral protease (RVP)-like domain along with other domains. The severity of opportunistic infections, caused by parasitic protozoa in AIDS patients, was found to decline when HIV protease inhibitors were used in antiretroviral therapy. Parasite growth was shown to be suppressed by a few of the inhibitors targeting Ddi1 present in these parasites. In this study, the binding of HIV protease inhibitors to the RVP domain of Ddi1 from <em>Toxoplasma gondii</em> and <em>Cryptosporidium hominis</em>; and the binding of ubiquitin to the ubiquitin-associated domain of Ddi1 from these two parasites were established using Biolayer Interferometry. The crystal structures of the RVP domains of Ddi1 from <em>T. gondii</em> and <em>C. hominis</em> were determined; they form homodimers similar to those observed in HIV protease and the reported structures of the same domain from <em>Saccharomyces cerevisiae</em>, <em>Leishmania major</em> and humans. The native form of the domain showed an open dimeric structure and a normal mode analysis revealed that it can take up a closed conformation resulting from relative movements of the subunits. Based on the crystal structure of the RVP domain of Ddi1 from <em>L. major</em>, a seven residue peptide inhibitor was designed and it was shown to bind to the RVP domain of Ddi1 from <em>L. major</em> by Biolayer Interferometry. This peptide was modified using computational methods and was shown to have a better affinity than the initial peptide.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 175-191"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000150/pdfft?md5=71c62a69e55ec00d3ea56e5e57a30aac&pid=1-s2.0-S2665928X22000150-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48203627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crystal structure of plasmoredoxin, a redox-active protein unique for malaria parasites","authors":"Karin Fritz-Wolf ,&nbsp;Jochen Bathke ,&nbsp;Stefan Rahlfs ,&nbsp;Katja Becker","doi":"10.1016/j.crstbi.2022.03.004","DOIUrl":"10.1016/j.crstbi.2022.03.004","url":null,"abstract":"<div><p>Plasmoredoxin is a 22 ​kDa thiol–disulfide oxidoreductase involved in cellular redox regulatory processes and antioxidant defense. The 1.6 ​Å structure of the protein, solved via X-ray crystallography, adopts a modified thioredoxin fold. The structure reveals that plasmoredoxin, unique for malarial parasites, forms a new subgroup of thioredoxin-like proteins together with tryparedoxin, unique for kinetoplastids. Unlike most members of this superfamily, Plrx does not have a proline residue within the CxxC redox motif. In addition, the Plrx structure has a distinct C-terminal domain. Similar to human thioredoxin, plasmoredoxin forms monomers and dimers, which are also structurally similar to the human thioredoxin dimer, and, as in humans, plasmoredoxin is inactive as a dimer. Monomer–dimer equilibrium depends on the surrounding redox conditions, which could support the parasite in reacting to oxidative challenges. Based on structural considerations, the residues of the dimer interface are likely to interact with target proteins. In contrast to <em>human</em> and <em>Plasmodium falciparum</em> thioredoxin, however, there is a cluster of positively charged residues at the dimer interface of plasmoredoxin. These intersubunit (lysine) residues might allow binding of the protein to cellular membranes or to plasminogen. Malaria parasites lack catalase and glutathione peroxidase and therefore depend on their other glutathione and thioredoxin-dependent redox relays. Plasmoredoxin could be part of a so far unknown electron transfer system that only occurs in these parasites. Since the surface charge of plasmoredoxin differs significantly from other members of the thioredoxin superfamily, its three-dimensional structure can provide a model for designing selective redox-modulatory inhibitors.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 87-95"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000083/pdfft?md5=35e1363adb6c298eb202cea0c5605a65&pid=1-s2.0-S2665928X22000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44193761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding structural variability in proteins using protein structural networks","authors":"Vasam Manjveekar Prabantu ,&nbsp;Vasundhara Gadiyaram ,&nbsp;Saraswathi Vishveshwara ,&nbsp;Narayanaswamy Srinivasan","doi":"10.1016/j.crstbi.2022.04.002","DOIUrl":"10.1016/j.crstbi.2022.04.002","url":null,"abstract":"<div><p>Proteins perform their function by accessing a suitable conformer from the ensemble of available conformations. The conformational diversity of a chosen protein structure can be obtained by experimental methods under different conditions. A key issue is the accurate comparison of different conformations. A gold standard used for such a comparison is the root mean square deviation (RMSD) between the two structures. While extensive refinements of RMSD evaluation at the backbone level are available, a comprehensive framework including the side chain interaction is not well understood. Here we employ protein structure network (PSN) formalism, with the non-covalent interactions of side chain, explicitly treated. The PSNs thus constructed are compared through graph spectral method, which provides a comparison at the local and at the global structural level. In this work, PSNs of multiple crystal conformers of single-chain, single-domain proteins, are subject to pair-wise analysis to examine the dissimilarity in their network topologies and in order to determine the conformational diversity of their native structures. This information is utilized to classify the structural domains of proteins into different categories. It is observed that proteins typically tend to retain structure and interactions at the backbone level. However, some of them also depict variability in either their overall structure or only in their inter-residue connectivity at the sidechain level, or both. Variability of sub-networks based on solvent accessibility and secondary structure is studied. The types of specific interactions are found to contribute differently to structure variability. An ensemble analysis by computing the mathematical variance of edge-weights across multiple conformers provided information on the contribution to overall variability from each edge of the PSN. Interactions that are highly variable are identified and their impact on structure variability has been discussed with the help of a case study. The classification based on the present side-chain network-based studies provides a framework to correlate the structure-function relationships in protein structures.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 134-145"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000101/pdfft?md5=64d94ec2e702d1f1be07d6d65c5a871e&pid=1-s2.0-S2665928X22000101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49479035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative computational and experimental analyses of some natural small molecules to restore transcriptional activation function of p53 in cancer cells harbouring wild type and p53Ser46 mutant","authors":"Seyad Shefrin ,&nbsp;Anissa Nofita Sari ,&nbsp;Vipul Kumar ,&nbsp;Huayue Zhang ,&nbsp;Hazna Noor Meidinna ,&nbsp;Sunil C. Kaul ,&nbsp;Renu Wadhwa ,&nbsp;Durai Sundar","doi":"10.1016/j.crstbi.2022.09.002","DOIUrl":"10.1016/j.crstbi.2022.09.002","url":null,"abstract":"<div><p>Genetic mutations in p53 are frequently associated with many types of cancers that affect its stability and activity through multiple ways. The Ser46 residue present in the transactivation domain2 (TAD2) domain of p53 undergoes phosphorylation that blocks its degradation by MDM2 and leads to cell cycle arrest/apoptosis/necrosis upon intrinsic or extrinsic stresses. On the other hand, unphosphorylated p53 mutants escape cell arrest or death triggered by these molecular signaling axes and lead to carcinogenesis. Phosphorylation of Ser in the TAD2 domain of p53 mediates its interactions with transcription factor p62, yielding transcriptional activation of downstream pro-apoptotic genes. The p53 phosphorylation causes string-like elongated conformation that increases its binding affinity with the PH domain of p62. On the other hand, lack of phosphorylation causes helix-like motifs and low binding affinity to p62. We undertook molecular simulation analyses to investigate the potential of some natural small molecules (Withanone (Wi-N) &amp; Withaferin-A (Wi-A) from Ashwagandha; Cucurbitacin-B (Cuc-B) from bitter Cucumber; and Caffeic acid phenethyl ester (CAPE) and Artepillin C (ARC) from honeybee propolis) to interact with p62-binding region of p53 and restore its wild-type activity. We found that Wi-N, Wi-A, and Cuc-B have the potential to restore p53-p62 interaction for phosphorylation-deficient p53 mutants. Wi-N, in particular, caused a reversal of the α-helical structure into an elongated string-like conformation similar to the wild-type p53. These data suggested the use of these natural compounds for the treatment of p53^Ser46 mutant harbouring cancers. We also compared the efficiency of Wi-N, Wi-A, Cuc-B, CAPE, and ARC to abrogate Mortalin-p53 binding resulting in nuclear translocation and reactivation of p53 function and provide experimental evidence to the computational analysis. Taken together, the use of these small molecules for reactivation of p53 in cancer cells is suggested.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 320-331"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9507986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40377922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel structural insights for a pair of monoclonal antibodies recognizing non-overlapping epitopes of the glucosyltransferase domain of Clostridium difficile toxin B","authors":"Jinyu Liu ,&nbsp;Michael Kothe ,&nbsp;Jianxin Zhang ,&nbsp;Eliud Oloo ,&nbsp;Svetlana Stegalkina ,&nbsp;Sophia T. Mundle ,&nbsp;Lu Li ,&nbsp;Jinrong Zhang ,&nbsp;Leah E. Cole ,&nbsp;Lucianna Barone ,&nbsp;Hans-Peter Biemann ,&nbsp;Harry Kleanthous ,&nbsp;Natalie G. Anosova ,&nbsp;Stephen F. Anderson","doi":"10.1016/j.crstbi.2022.03.003","DOIUrl":"10.1016/j.crstbi.2022.03.003","url":null,"abstract":"<div><p><em>Clostridium difficile</em> toxins are the primary causative agents for hospital-acquired diarrhea and pseudomembranous colitis. Numerous monoclonal antibodies (mAbs) targeting different domains of <em>Clostridium difficile</em> toxin have been reported. Here we report the crystal structures of two mAbs, B1 and B2, in complex with the glycosyltransferase domain (GTD) of the <em>Clostridium difficile</em> toxin B (TcdB). B2 bound to the N-terminal 4 helix bundle of the GTD, a conserved membrane localization domain (MLD) found in the large clostridial glycosylating toxin family implicated in targeting plasma membrane. B1 bound to a distinct epitope at the hinge region between the MLD and the catalytic subdomain of the GTD. Functional studies revealed the potency of these mAbs <em>in vitro</em> and <em>in vivo</em> to be synergistic when given in combination.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 96-105"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000071/pdfft?md5=4a4136597a850e24f49d0aeffaad03e7&pid=1-s2.0-S2665928X22000071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46043093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insight into the nucleoside transport and inhibition of human ENT1","authors":"Zhixiang Wu ,&nbsp;Zhongjie Han ,&nbsp;Wenxue Zhou ,&nbsp;Xiaohan Sun ,&nbsp;Lei Chen ,&nbsp;Shuang Yang ,&nbsp;Jianping Hu ,&nbsp;Chunhua Li","doi":"10.1016/j.crstbi.2022.05.005","DOIUrl":"10.1016/j.crstbi.2022.05.005","url":null,"abstract":"<div><p>The human equilibrative nucleoside transporter 1 (hENT1) is an effective controller of adenosine signaling by regulating its extracellular and intracellular concentration, and has become a solid drug target of clinical used adenosine reuptake inhibitors (AdoRIs). Currently, the mechanisms of adenosine transport and inhibition for hENT1 remain unclear, which greatly limits the in-depth understanding of its inner workings as well as the development of novel inhibitors. In this work, the dynamic details of hENT1 underlie adenosine transport and the inhibition mechanism of the non-nucleoside AdoRIs dilazep both were investigated by comparative long-time unbiased molecular dynamics simulations. The calculation results show that the conformational transitions of hENT1 from the outward open to metastable occluded state are mainly driven by TM1, TM2, TM7 and TM9. One of the trimethoxyphenyl rings in dilazep serves as the adenosyl moiety of the endogenous adenosine substrate to competitively occupy the orthosteric site of hENT1. Due to extensive and various <em>VDW</em> interactions with N30, M33, M84, P308 and F334, the other trimethoxyphenyl ring is stuck in the opportunistic site near the extracellular side preventing the complete occlusion of thin gate simultaneously. Obviously, dilazep shows significant inhibitory activity by disrupting the local induce-fit action in substrate binding cavity and blocking the transport cycle of whole protein. This study not only reveals the nucleoside transport mechanism by hENT1 at atomic level, but also provides structural guidance for the subsequent design of novel non-nucleoside AdoRIs with enhanced pharmacologic properties.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 192-205"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X22000174/pdfft?md5=e1c75ea5b8ad5a522cd8b2abcc83a0c3&pid=1-s2.0-S2665928X22000174-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46964148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted membrane binding head of the SARS-CoV-2 spike protein","authors":"Anh Tran,&nbsp;Troy A. Kervin,&nbsp;Michael Overduin","doi":"10.1016/j.crstbi.2022.05.001","DOIUrl":"10.1016/j.crstbi.2022.05.001","url":null,"abstract":"<div><p>The SARS-CoV-2 spike protein presents a surface with enormous membrane binding potential to host tissues and organelles of infected cells. Its exposed trimeric head binds not only the angiotensin-converting enzyme 2 (ACE2), but also host phospholipids which are missing from all existing structures. Hence, the membrane interaction surfaces that mediate viral fusion, entry, assembly and egress remain unclear. Here the spike:membrane docking sites are identified based on membrane optimal docking area (MODA) analysis of 3D structures of spike proteins in closed and open conformations at endocytic and neutral pH levels as well as ligand complexes. This reveals multiple membrane binding sites in the closed spike head that together prefer convex membranes and are modulated by pH, fatty acids and post-translational modifications including glycosylation. The exposure of the various membrane interaction sites adjusts upon domain repositioning within the trimer, allowing formation of intermediate bilayer complexes that lead to the prefusion state while also enabling ACE2 receptor recognition. In contrast, all antibodies that target the spike head would block the membrane docking process that precedes ACE2 recognition. Together this illuminates the engagements of the spike protein with plasma, endocytic, ER or exocytic vesicle membranes that help to drive the cycle of viral infection, and offers novel sites for intervention.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 146-157"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49007296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular docking and simulation of IcaC protein as O-succinyltransferase function in staphylococcus epidermidis biofilm formation","authors":"Ramachandira Prabu ,&nbsp;Amaresh Mohanty ,&nbsp;Susmida Seni Balakrishnan ,&nbsp;G. Jayalakshmi ,&nbsp;Kothandapani Sundar","doi":"10.1016/j.crstbi.2022.03.002","DOIUrl":"10.1016/j.crstbi.2022.03.002","url":null,"abstract":"<div><p>Intercellular adhesion (IcaADBC) operon is necessary for PNAG (Polyβ-1,6-N-acetyl-D-glucosamine) biosynthesis of biofilm formation in <em>Staphylococcus epidermidis</em>. IcaC protein has a wide range of functions in terms of growth phase variation, migration, transposon insertion, PNAG modification, biofilm formation. Unusual TTTA signature motifs were identified from nucleotide sequence. Asparagine-linked glycosylation consensus motifs were identified at position 169 and 240. <em>S</em>. <em>epidermidis</em> was a close evolutionary association with <em>S</em>. <em>haemolyticus</em> and other <em>Staphylococcus</em> spp. Due to the non-availability of crystal structure, protein threading procedure was selected for constructing a full length IcaC three-dimensional structure. QMEANBrane structure quality assessment with model scores −100000 range within predicted integral membrane structure. IcaC motif constitutes 18 transmembrane helix, 37 helix-helix interaction, 8 beta turn, 2 gamma turn. Binding free energy was calculated with their succinate ligand docking form hydrogen bond with critical amino acids showed ΔG score −2.574 ​kJ/mol using Schrödinger. Serine (Ser96), Glutamic acid (Glu99), Tryptophan (Trp191) were active site amino acids form the catalytic core required for O-succinyltransferase function. Molecular dynamics simulation (MDS) was performed to evaluate the stability of IcaC protein and IcaC-Succinate binding complexes with the active site amino acids throughout trajectories captured with time scale 100 ns simulation period using GROMACS 4.5.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 78-86"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X2200006X/pdfft?md5=b2be9e8a0290b02be1d65323939b1627&pid=1-s2.0-S2665928X2200006X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42035642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amyloid management by chaperones: The mystery underlying protein oligomers’ dual functions","authors":"Payam Arghavani,&nbsp;Mitra Pirhaghi,&nbsp;Faezeh Moosavi-Movahedi,&nbsp;Fatemeh Mamashli,&nbsp;Elnaz Hosseini,&nbsp;Ali Akbar Moosavi-Movahedi","doi":"10.1016/j.crstbi.2022.11.002","DOIUrl":"10.1016/j.crstbi.2022.11.002","url":null,"abstract":"<div><p>Protein oligomerization has two notable aspects: it is crucial for the performing cellular and molecular processes accurately, and it produces amyloid fibril precursors. Although a clear explanation for amyloidosis as a whole is lacking, most studies have emphasized the importance of protein misfolding followed by formation of cytotoxic oligomer structures, which are responsible for disorders as diverse as neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and metabolic disorders, such as type 2 diabetes. Constant surveillance by oligomeric protein structures known as molecular chaperones enables cells to overcome the challenge of misfolded proteins and their harmful assemblies. These molecular chaperones encounter proteins in cells, and benefit cell survival as long as they perform correctly. Thus, this review highlights the roles of structural aspects of chaperone protein oligomers in determining cell fate—either succumbing to amyloid oligomers or survival—as well as experimental approaches used to investigate these entities.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":"4 ","pages":"Pages 356-364"},"PeriodicalIF":2.8,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10713287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}