+検索条件
-Structure paper
タイトル | Conformational dynamics of the Beta and Kappa SARS-CoV-2 spike proteins and their complexes with ACE2 receptor revealed by cryo-EM. |
---|---|
ジャーナル・号・ページ | Nat Commun, Vol. 12, Issue 1, Page 7345, Year 2021 |
掲載日 | 2021年12月20日 |
著者 | Yifan Wang / Cong Xu / Yanxing Wang / Qin Hong / Chao Zhang / Zuyang Li / Shiqi Xu / Qinyu Zuo / Caixuan Liu / Zhong Huang / Yao Cong / |
PubMed 要旨 | The emergence of SARS-CoV-2 Kappa and Beta variants with enhanced transmissibility and resistance to neutralizing antibodies has created new challenges for the control of the ongoing COVID-19 ...The emergence of SARS-CoV-2 Kappa and Beta variants with enhanced transmissibility and resistance to neutralizing antibodies has created new challenges for the control of the ongoing COVID-19 pandemic. Understanding the structural nature of Kappa and Beta spike (S) proteins and their association with ACE2 is of significant importance. Here we present two cryo-EM structures for each of the Kappa and Beta spikes in the open and open-prone transition states. Compared with wild-type (WT) or G614 spikes, the two variant spikes appear more untwisted/open especially for Beta, and display a considerable population shift towards the open state as well as more pronounced conformational dynamics. Moreover, we capture four conformational states of the S-trimer/ACE2 complex for each of the two variants, revealing an enlarged conformational landscape for the Kappa and Beta S-ACE2 complexes and pronounced population shift towards the three RBDs up conformation. These results implicate that the mutations in Kappa and Beta may modify the kinetics of receptor binding and viral fusion to improve virus fitness. Combined with biochemical analysis, our structural study shows that the two variants are enabled to efficiently interact with ACE2 receptor despite their sensitive ACE2 binding surface is modified to escape recognition by some potent neutralizing MAbs. Our findings shed new light on the pathogenicity and immune evasion mechanism of the Beta and Kappa variants. |
リンク | Nat Commun / PubMed:34930910 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 4.0 Å |
構造データ | EMDB-32167, PDB-7vx1: EMDB-32168, PDB-7vx4: EMDB-32169, PDB-7vx5: EMDB-32170: SARS-CoV-2 Beta variant spike protein in transition state EMDB-32172, PDB-7vx9: EMDB-32173, PDB-7vxa: EMDB-32174, PDB-7vxb: EMDB-32175, PDB-7vxc: EMDB-32176, PDB-7vxd: EMDB-32177, PDB-7vxe: EMDB-32178, PDB-7vxf: EMDB-32180, PDB-7vxi: EMDB-32182, PDB-7vxk: EMDB-32184, PDB-7vxm: |
化合物 | ChemComp-ZN: ChemComp-NAG: |
由来 |
|
キーワード | VIRAL PROTEIN / SARS-CoV-2 / coronavirus / Beta variant / B.1.351 lineage / spike protein / Angiotensin-converting enzyme 2 / Kappa variant / B.1.617.1 lineage / VIRAL PROTEIN/HYDROLASE / VIRAL PROTEIN-HYDROLASE complex / SPIK PROTEIN |