Structural Comparison of the SARS CoV 2 Spike Protein Relative to Other Human-Infecting Coronaviruses.
Structural Comparison of the SARS CoV 2 Spike Protein Relative to Other Human-Infecting Coronaviruses.
复制标题
DOI：
10.3389/fmed.2020.594439
复制
发表时间：
2020
影响因子：
3.9
通讯作者：
Imai K
中科院分区：
文献类型：
--
作者：
Cueno ME;Imai K
冠状病毒(CoV)是一种包膜的正链RNA病毒，历史上已知有七种具有不同毒力的人类感染CoV。冠状病毒对宿主的附着是病毒致病的第一步，主要依赖于病毒表面的刺突糖蛋白。在人类感染的冠状病毒中，只有SARS CoV 2(SARS2)在人类中的感染导致了大流行，这表明SARS2刺突蛋白的蛋白质结构构象与其他人感染的冠状病毒不同。令人惊讶的是，不同的人类感染冠状病毒刺突蛋白之间在蛋白质结构构象上的可能的差异和相似之处还没有完全阐明。在这项研究中，我们利用计算方法建立了模型并分析了七种人类感染的CoV Spike蛋白，即：hCoV 229E、HCoV OC43、HCoV NL63、HCoV HKU1、SARS CoV、MERS CoV和SARS2。对所生成的所有冠状病毒模型进行模型质量评估，对整个蛋白质模型和选定的S1结构域(S1-CTD和S1-NTD)进行结构叠加，并基于RMSD值、TM评分和接触图谱进行结构比较。我们发现，S1-CTD的结构取向是一个与冠状病毒系统发育簇和谱系相关的潜在结构特征。此外，我们观察到，同一系统发育簇或谱系中的SPEK模型可能具有相似的蛋白质结构。此外，我们还证实了在感染人类的冠状病毒中可能存在三种不同的S1-CTD取向(模式I、模式II、模式III)。此外，我们推测，同一系统发育簇中的人类感染冠状病毒可能具有相似的S1-CTD和S1-NTD结构取向。综上所述，我们认为SARS2棘突S1-CTD遵循模式III，与SARS1有较高的相似性，与OC43和HKU1有一定程度的相似性，OC43和HKU1恰好位于相同的系统发育簇和谱系中，而SARS2棘突S1-NTD在同一系统发育簇或谱系中的人类感染冠状病毒之间有一定程度的相似性。
Coronaviruses (CoV) are enveloped positive-stranded RNA viruses and, historically, there are seven known human-infecting CoVs with varying degrees of virulence. CoV attachment to the host is the first step of viral pathogenesis and mainly relies on the spike glycoprotein located on the viral surface. Among the human-infecting CoVs, only the infection of SARS CoV 2 (SARS2) among humans resulted to a pandemic which would suggest that the protein structural conformation of SARS2 spike protein is distinct as compared to other human-infecting CoVs. Surprisingly, the possible differences and similarities in the protein structural conformation between the various human-infecting CoV spike proteins have not been fully elucidated. In this study, we utilized a computational approach to generate models and analyze the seven human-infecting CoV spike proteins, namely: HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV, and SARS2. Model quality assessment of all CoV models generated, structural superimposition of the whole protein model and selected S1 domains (S1-CTD and S1-NTD), and structural comparison based on RMSD values, Tm scores, and contact mapping were all performed. We found that the structural orientation of S1-CTD is a potential structural feature associated to both the CoV phylogenetic cluster and lineage. Moreover, we observed that spike models in the same phylogenetic cluster or lineage could potentially have similar protein structure. Additionally, we established that there are potentially three distinct S1-CTD orientation (Pattern I, Pattern II, Pattern III) among the human-infecting CoVs. Furthermore, we postulate that human-infecting CoVs in the same phylogenetic cluster may have similar S1-CTD and S1-NTD structural orientation. Taken together, we propose that the SARS2 spike S1-CTD follows a Pattern III orientation which has a higher degree of similarity with SARS1 and some degree of similarity with both OC43 and HKU1 which coincidentally are in the same phylogenetic cluster and lineage, whereas, the SARS2 spike S1-NTD has some degree of similarity among human-infecting CoVs that are either in the same phylogenetic cluster or lineage.
登录
查看更多内容
影响因子：
--
作者：
Hulswit RJ;de Haan CA;Bosch BJ
通讯作者：
Bosch BJ
影响因子：
4.6
作者：
Bittrich, Sebastian;Schroeder, Michael;Labudde, Dirk
通讯作者：
Labudde, Dirk
影响因子：
9.4
作者：
Dijkman, Ronald;Jebbink, Maarten F.;van der Hoek, Lia
通讯作者：
van der Hoek, Lia
影响因子：
11.8
作者：
Chiu, SS;Chan, KH;Peiris, JSM
通讯作者：
Peiris, JSM
DOI：
10.1128/cdli.12.11.1317-1321.2005
发表时间：
2005-11-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Chan, KH;Cheng, VCC;Peiris, JSM
通讯作者：
Peiris, JSM