Journal of structural biology最新文献

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Dual pattern of cholesterol-induced decoupling of residue-residue interactions of Kir2.2 胆固醇诱导 Kir2.2 的残基-残基相互作用解耦的双重模式
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-04-17 DOI: 10.1016/j.jsb.2024.108091
Katie M. Beverley , Nicolas Barbera , Irena Levitan
{"title":"Dual pattern of cholesterol-induced decoupling of residue-residue interactions of Kir2.2","authors":"Katie M. Beverley ,&nbsp;Nicolas Barbera ,&nbsp;Irena Levitan","doi":"10.1016/j.jsb.2024.108091","DOIUrl":"https://doi.org/10.1016/j.jsb.2024.108091","url":null,"abstract":"<div><p>Cholesterol is a negative regulator of a variety of ion channels. We have previously shown that cholesterol suppresses Kir2.2 channels via residue-residue uncoupling on the inter-subunit interfaces within the close state of the channels (3JYC). In this study, we extend this analysis to the other known structure of Kir2.2 that is closer to the open state of Kir2.2 channels (3SPI) and provide additional analysis of the residue distances between the uncoupled residues and cholesterol binding domains in the two conformation states of the channels. We found that the general phenomenon of cholesterol binding leading to uncoupling between specific residues is conserved in both channel states but the specific pattern of the uncoupling residues is distinct between the two states and implies different mechanisms. Specifically, we found that cholesterol binding in the 3SPI state results in an uncoupling of residues in three distinct regions; the transmembrane domain, membrane-cytosolic interface, and the cytosolic domain, with the first two regions forming an envelope around PI(4,5)P2 and cholesterol binding sites and the distal region overlapping with the subunit-subunit interface characterized in our previous study of the disengaged state. We also found that this uncoupling is dependent upon the number of cholesterol molecules bound to the channel. We further generated a mutant channel Kir2.2<sup>P187V</sup> with a single point mutation in a residue proximal to the PI(4,5)P2 binding site, which is predicted to be uncoupled from other residues in its vicinity upon cholesterol binding and found that this mutation abrogates the sensitivity of Kir2.2 to cholesterol changes in the membrane. These findings suggest that cholesterol binding to this conformation state of Kir2.2 channels may destabilize the PI(4,5)P2 interactions with the channels while in the disengaged state the destabilization occurs where the subunits interact. These findings give insight into the structural mechanistic basis for the functional effects of cholesterol binding to the Kir2.2 channel.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy 在散发性和荷兰型脑淀粉样血管病中,静电簇引导 Aβ40 纤维的形成
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-04-13 DOI: 10.1016/j.jsb.2024.108092
Ziao Fu , Elliot J. Crooks , Brandon A. Irizarry , Xiaoyue Zhu , Saikat Chowdhury , William E. Van Nostrand , Steven O. Smith
{"title":"An electrostatic cluster guides Aβ40 fibril formation in sporadic and Dutch-type cerebral amyloid angiopathy","authors":"Ziao Fu ,&nbsp;Elliot J. Crooks ,&nbsp;Brandon A. Irizarry ,&nbsp;Xiaoyue Zhu ,&nbsp;Saikat Chowdhury ,&nbsp;William E. Van Nostrand ,&nbsp;Steven O. Smith","doi":"10.1016/j.jsb.2024.108092","DOIUrl":"https://doi.org/10.1016/j.jsb.2024.108092","url":null,"abstract":"<div><p>Cerebral amyloid angiopathy (CAA) is associated with the accumulation of fibrillar Aβ peptides upon and within the cerebral vasculature, which leads to loss of vascular integrity and contributes to disease progression in Alzheimer’s disease (AD). We investigate the structure of human-derived Aβ40 fibrils obtained from patients diagnosed with sporadic or familial Dutch-type (E22Q) CAA. Using cryo-EM, two primary structures are identified containing elements that have not been observed in <em>in vitro</em> Aβ40 fibril structures. One population has an ordered N-terminal fold comprised of two β-strands stabilized by electrostatic interactions involving D1, E22, D23 and K28. This charged cluster is disrupted in the second population, which exhibits a disordered N-terminus and is favored in fibrils derived from the familial Dutch-type CAA patient. These results illustrate differences between human-derived CAA and AD fibrils, and how familial CAA mutations can guide fibril formation.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1047847724000327/pdfft?md5=40eb245f121be7c4952bc3bc62c89872&pid=1-s2.0-S1047847724000327-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cryo-EM structure of bacterial nitrilase reveals insight into oligomerization, substrate recognition, and catalysis 细菌硝化酶的低温电子显微镜结构揭示了寡聚化、底物识别和催化作用的奥秘
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-04-13 DOI: 10.1016/j.jsb.2024.108093
Sergio Aguirre-Sampieri , Ana Casañal , Paul Emsley , Georgina Garza-Ramos
{"title":"Cryo-EM structure of bacterial nitrilase reveals insight into oligomerization, substrate recognition, and catalysis","authors":"Sergio Aguirre-Sampieri ,&nbsp;Ana Casañal ,&nbsp;Paul Emsley ,&nbsp;Georgina Garza-Ramos","doi":"10.1016/j.jsb.2024.108093","DOIUrl":"https://doi.org/10.1016/j.jsb.2024.108093","url":null,"abstract":"<div><p>Many enzymes can self-assemble into higher-order structures with helical symmetry. A particularly noteworthy example is that of nitrilases, enzymes in which oligomerization of dimers into spiral homo-oligomers is a requirement for their enzymatic function. Nitrilases are widespread in nature where they catalyze the hydrolysis of nitriles into the corresponding carboxylic acid and ammonia. Here, we present the Cryo-EM structure, at 3 Å resolution, of a C-terminal truncate nitrilase from <em>Rhodococcus</em> sp. V51B that assembles in helical filaments. The model comprises a complete turn of the helical arrangement with a substrate-intermediate bound to the catalytic cysteine. The structure was solved having added the substrate to the protein. The length and stability of filaments was made more substantial in the presence of the aromatic substrate, benzonitrile, but not for aliphatic nitriles or dinitriles. The overall structure maintains the topology of the nitrilase family, and the filament is formed by the association of dimers in a chain-like mechanism that stabilizes the spiral. The active site is completely buried inside each monomer, while the substrate binding pocket was observed within the oligomerization interfaces. The present structure is in a closed configuration, judging by the position of the lid, suggesting that the intermediate is one of the covalent adducts. The proximity of the active site to the dimerization and oligomerization interfaces, allows the dimer to sense structural changes once the benzonitrile was bound, and translated to the rest of the filament, stabilizing the helical structure.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1047847724000339/pdfft?md5=47ad576135cc948b9dab3bbfca52d616&pid=1-s2.0-S1047847724000339-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Correlating cryo-super resolution radial fluctuations and dual-axis cryo-scanning transmission electron tomography to bridge the light-electron resolution gap” [J. Struct. Biol. 215 (2023) 107982] 低温超分辨率径向波动与双轴低温扫描透射电子断层扫描的相关性弥合光-电子分辨率差距》[J. Struct.
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-30 DOI: 10.1016/j.jsb.2024.108085
Peter Kirchweger , Debakshi Mullick , Prabhu Prasad Swain , Sharon G. Wolf , Michael Elbaum
{"title":"Corrigendum to “Correlating cryo-super resolution radial fluctuations and dual-axis cryo-scanning transmission electron tomography to bridge the light-electron resolution gap” [J. Struct. Biol. 215 (2023) 107982]","authors":"Peter Kirchweger ,&nbsp;Debakshi Mullick ,&nbsp;Prabhu Prasad Swain ,&nbsp;Sharon G. Wolf ,&nbsp;Michael Elbaum","doi":"10.1016/j.jsb.2024.108085","DOIUrl":"https://doi.org/10.1016/j.jsb.2024.108085","url":null,"abstract":"","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S104784772400025X/pdfft?md5=42332a4dd8dca3ab8b5fc14f9edabd5e&pid=1-s2.0-S104784772400025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140330754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Crystal structure of the Mycobacterium tuberculosis VirS regulator reveals its interaction with the lead compound SMARt751 结核分枝杆菌 VirS 调节器的晶体结构揭示了它与先导化合物 SMARt751 的相互作用。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-26 DOI: 10.1016/j.jsb.2024.108090
Camille Grosse , Maud Sigoillot , Véronique Megalizzi , Abdalkarim Tanina , Nicolas Willand , Alain R. Baulard , René Wintjens
{"title":"Crystal structure of the Mycobacterium tuberculosis VirS regulator reveals its interaction with the lead compound SMARt751","authors":"Camille Grosse ,&nbsp;Maud Sigoillot ,&nbsp;Véronique Megalizzi ,&nbsp;Abdalkarim Tanina ,&nbsp;Nicolas Willand ,&nbsp;Alain R. Baulard ,&nbsp;René Wintjens","doi":"10.1016/j.jsb.2024.108090","DOIUrl":"10.1016/j.jsb.2024.108090","url":null,"abstract":"<div><p>Ethionamide (ETO) is a prodrug that is primarily used as a second-line agent in the treatment of tuberculosis. Among the bacterial ETO activators, the monooxygenase MymA has been recently identified, and its expression is regulated by the mycobacterial regulator VirS. The discovery of VirS ligands that can enhance <em>mymA</em> expression and thereby increase the antimycobacterial efficacy of ETO, has led to the development of a novel therapeutic strategy against tuberculosis. This strategy involves the selection of preclinical candidates, including SMARt751. We report the first crystal structure of the AraC-like regulator VirS, in complex with SMARt751, refined at 1.69 Å resolution. Crystals were obtained via an <em>in situ</em> proteolysis method in the requisite presence of SMARt751. The elucidated structure corresponds to the ligand-binding domain of VirS, adopting an α/β fold with structural similarities to H-NOX domains. Within the VirS structure, SMARt751 is situated in a completely enclosed hydrophobic cavity, where it forms hydrogen bonds with Asn11 and Asn149 as well as van der Waals contacts with various hydrophobic amino acids. Comprehensive structural comparisons within the AraC family of transcriptional regulators are conducted and analyzed to figure out the effects of the SMARt751 binding on the regulatory activity of VirS.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Unveiling success determinants for AMB-assisted phase expansion of fusion proteins in ARP/wARP 揭示 ARP/wARP 中 AMB 辅助相扩增融合蛋白的成功决定因素。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-26 DOI: 10.1016/j.jsb.2024.108089
María C. Cardona-Echavarría , Carmen Santillán , Ricardo Miranda-Blancas , Vivian Stojanoff , Enrique Rudiño-Piñera
{"title":"Unveiling success determinants for AMB-assisted phase expansion of fusion proteins in ARP/wARP","authors":"María C. Cardona-Echavarría ,&nbsp;Carmen Santillán ,&nbsp;Ricardo Miranda-Blancas ,&nbsp;Vivian Stojanoff ,&nbsp;Enrique Rudiño-Piñera","doi":"10.1016/j.jsb.2024.108089","DOIUrl":"10.1016/j.jsb.2024.108089","url":null,"abstract":"<div><p>Fusion proteins (FPs) are frequently utilized as a biotechnological tool in the determination of macromolecular structures using X-ray methods. Here, we explore the use of different protein tags in various FP, to obtain initial phases by using them in a partial molecular replacement (MR) and constructing the remaining FP structure with ARP/wARP. Usually, the tag is removed prior to crystallization, however leaving the tag on may facilitate crystal formation, and structural determination by expanding phases from known to unknown segments of the complex. In this study, the Protein Data Bank was mined for an up-to-date list of FPs with the most used protein tags, Maltose Binding Protein (MBP), Green Fluorescent Protein (GFP), Thioredoxin (TRX), Glutathione transferase (GST) and the Small Ubiquitin-like Modifier Protein (SUMO). Partial MR using the protein tag, followed by automatic model building, was tested on a subset of 116 FP. The efficiency of this method was analyzed and factors that influence the coordinate construction of a substantial portions of the fused protein were identified. Using MBP, GFP, and SUMO as phase generators it was possible to build at least 75 % of the protein of interest in 36 of the 116 cases tested. Our results reveal that tag selection has a significant impact; tags with greater structural stability, such as GFP, increase the success rate. Further statistical analysis identifies that resolution, Wilson B factor, solvent percentage, completeness, multiplicity, protein tag percentage in the FP (considering amino acids), and the linker length play pivotal roles using our approach. In cases where a structural homologous is absent, this method merits inclusion in the toolkit of protein crystallographers.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140306058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Structural and kinetic analysis of the monofunctional Staphylococcus aureus PBP1 单功能金黄色葡萄球菌 PBP1 的结构和动力学分析。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-26 DOI: 10.1016/j.jsb.2024.108086
Christopher G. Bon , Jason C. Grigg , Jaeyong Lee , Craig S. Robb , Nathanael A. Caveney , Lindsay D. Eltis , Natalie C.J. Strynadka
{"title":"Structural and kinetic analysis of the monofunctional Staphylococcus aureus PBP1","authors":"Christopher G. Bon ,&nbsp;Jason C. Grigg ,&nbsp;Jaeyong Lee ,&nbsp;Craig S. Robb ,&nbsp;Nathanael A. Caveney ,&nbsp;Lindsay D. Eltis ,&nbsp;Natalie C.J. Strynadka","doi":"10.1016/j.jsb.2024.108086","DOIUrl":"10.1016/j.jsb.2024.108086","url":null,"abstract":"<div><p><em>Staphylococcus aureus</em>, an ESKAPE pathogen, is a major clinical concern due to its pathogenicity and manifold antimicrobial resistance mechanisms. The commonly used β-lactam antibiotics target bacterial penicillin-binding proteins (PBPs) and inhibit crosslinking of peptidoglycan strands that comprise the bacterial cell wall mesh, initiating a cascade of effects leading to bacterial cell death. <em>S. aureus</em> PBP1 is involved in synthesis of the bacterial cell wall during division and its presence is essential for survival of both antibiotic susceptible and resistant <em>S. aureus</em> strains. Here, we present X-ray crystallographic data for <em>S. aureus</em> PBP1 in its apo form as well as acyl-enzyme structures with distinct classes of β-lactam antibiotics representing the penicillins, carbapenems, and cephalosporins, respectively: oxacillin, ertapenem and cephalexin. Our structural data suggest that the PBP1 active site is readily accessible for substrate, with little conformational change in key structural elements required for its covalent acylation of β-lactam inhibitors. Stopped-flow kinetic analysis and gel-based competition assays support the structural observations, with even the weakest performing β-lactams still having comparatively high acylation rates and affinities for PBP1. Our structural and kinetic analysis sheds insight into the ligand–PBP interactions that drive antibiotic efficacy against these historically useful antimicrobial targets and expands on current knowledge for future drug design and treatment of <em>S. aureus</em> infections.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1047847724000261/pdfft?md5=90b179f904d39532e74640b54f53d324&pid=1-s2.0-S1047847724000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melanin granules morphology and distribution in human black hair investigated by focused ion beam scanning electron microscopy: Differences between Asian and Caucasian hair 用聚焦离子束扫描电子显微镜研究人类黑色头发中黑色素颗粒的形态和分布:亚洲人和白种人头发的差异。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-24 DOI: 10.1016/j.jsb.2024.108088
Toru Kojima , Hiromi Yamada , Sakiko Enomoto , Tomoyo Nakao , Shigeo Arai
{"title":"Melanin granules morphology and distribution in human black hair investigated by focused ion beam scanning electron microscopy: Differences between Asian and Caucasian hair","authors":"Toru Kojima ,&nbsp;Hiromi Yamada ,&nbsp;Sakiko Enomoto ,&nbsp;Tomoyo Nakao ,&nbsp;Shigeo Arai","doi":"10.1016/j.jsb.2024.108088","DOIUrl":"10.1016/j.jsb.2024.108088","url":null,"abstract":"<div><p>Melanin granules (melanosomes) in Asian and Caucasian black hairs were investigated by focused ion beam scanning electron microscopy (FIB-SEM). This technique facilitates a direct evaluation of the three-dimensional distribution and morphology of melanin granules without requiring their isolation from hair. Three-dimensional reconstructed images of melanin granule distribution in hair samples were obtained using serial SEM images observed by FIB-SEM. Melanin granules in black hair tended to be three-dimensionally dense in the outer periphery of the cortex. The morphometric parameters of melanin granules were calculated using the reconstructed three-dimensional images. The results confirmed that melanin granules in Caucasian black hair were much smaller those in Asian black hair. Moreover, it was indicated that the relative frequency distribution of the volume of melanin granules was significantly different between Asians and Caucasians.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Molecular insights into the binding interactions and energetics of the omicron spike variant with hACE2 and a neutralizing antibody 从分子角度揭示欧米克隆尖峰变体与 hACE2 和中和抗体的结合相互作用和能量学。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-16 DOI: 10.1016/j.jsb.2024.108087
Vipul Kumar , Seyad Shefrin, Durai Sundar
{"title":"Molecular insights into the binding interactions and energetics of the omicron spike variant with hACE2 and a neutralizing antibody","authors":"Vipul Kumar ,&nbsp;Seyad Shefrin,&nbsp;Durai Sundar","doi":"10.1016/j.jsb.2024.108087","DOIUrl":"10.1016/j.jsb.2024.108087","url":null,"abstract":"<div><p>The global spread of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) since 2019 has led to a continuous evolution of viral variants, with the latest concern being the Omicron (B.1.1.529) variant. In this study, classical molecular dynamics simulations were conducted to elucidate the biophysical aspects of the Omicron spike protein's receptor-binding domain (RBD) in its interaction with human angiotensin-converting enzyme 2 (hACE2) and a neutralizing antibody, comparing it to the wildtype (WT). To model the Omicron variant, 15 in silico mutations were introduced in the RBD region of WT (retrieved from PDB). The simulations of WT spike-hACE2 and Omicron spike-hACE2 complexes revealed comparable binding stability and dynamics. Notably, the Q493R mutation in the Omicron spike increased interactions with hACE2, particularly with ASP38 and ASP355. Additionally, mutations such as N417K, T478K, and Y505H contributed to enhanced structural stability in the Omicron variant. Conversely, when comparing WT with Omicron in complex with a neutralizing antibody, simulation results demonstrated poorer binding dynamics and stability for the Omicron variant. The E484K mutation significantly decreased binding interactions, resulting in an overall decrease in binding energy (∼−57 kcal/mol) compared to WT (∼−84 kcal/mol). This study provides valuable molecular insights into the heightened infectivity of the Omicron variant, shedding light on the specific mutations influencing its interactions with hACE2 and neutralizing antibodies.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimal 3D angular sampling with applications to cryo-EM problems 优化三维角度采样并应用于低温电子显微镜问题。
IF 3 3区 生物学
Journal of structural biology Pub Date : 2024-03-14 DOI: 10.1016/j.jsb.2024.108083
Valeriy Titarenko , Alan M. Roseman
{"title":"Optimal 3D angular sampling with applications to cryo-EM problems","authors":"Valeriy Titarenko ,&nbsp;Alan M. Roseman","doi":"10.1016/j.jsb.2024.108083","DOIUrl":"10.1016/j.jsb.2024.108083","url":null,"abstract":"<div><p>The goal of cryo-EM experiments in the biological sciences is to determine the atomic structure of a molecule and deduce insights into its functions and mechanisms. Despite improvements in instrumentation for data collection and new software algorithms, in most cases, individual atoms are not resolved. Model building of proteins, nucleic acids, or molecules in general, is feasible from the experimentally determined density maps at resolutions up to the range of 3–4 Angstroms. For lower-resolution maps or parts of maps, fitting smaller structures obtained by modelling or experimental techniques with higher resolution is a way to resolve the issue. In practice, we have an atomic structure, generate its density map at a given resolution, and translate/rotate the map within a region of interest in the experimental map, computing a measure-of-fit score with the corresponding areas of the experimental map. This procedure is computationally intensive since we work in 6D space. An optimal ordered list of rotations will reduce the angular error and help to find the best-fitting positions faster for a coarse global search or a local refinement. It can be used for adaptive approaches to stop fitting algorithms earlier once the desired accuracy has been achieved. We demonstrate how the performance of some fitting algorithms can be improved by grouping sets of rotations. We present an approach to generate more efficient 3D angular sampling, and provide the computer code to generate lists of optimal orientations for single and grouped rotations and the lists themselves.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1047847724000236/pdfft?md5=7e1e2d9ef741145f9751aeb796e70580&pid=1-s2.0-S1047847724000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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