Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM
The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an...
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| Veröffentlicht in: | Science advances 2021-01, Vol.7 (1) |
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| creator | Xu, Cong Wang, Yanxing Liu, Caixuan Zhang, Chao Han, Wenyu Hong, Xiaoyu Wang, Yifan Hong, Qin Wang, Shutian Zhao, Qiaoyu Wang, Yalei Yang, Yong Chen, Kaijian Zheng, Wei Kong, Liangliang Wang, Fangfang Zuo, Qinyu Huang, Zhong Cong, Yao |
| description | The recent outbreaks of SARS-CoV-2 pose a global health emergency. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics. |
| doi_str_mv | 10.1126/sciadv.abe5575 |
| format | Article |
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The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abe5575</identifier><identifier>PMID: 33277323</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Angiotensin-Converting Enzyme 2 - chemistry ; Animals ; Coronavirus ; Cryoelectron Microscopy ; Enzyme-Linked Immunosorbent Assay ; Humans ; Image Processing, Computer-Assisted ; Ligands ; Mice ; Mice, Inbred BALB C ; Mutation ; Peptides - chemistry ; Polysaccharides ; Principal Component Analysis ; Protein Binding ; Protein Domains ; SARS-CoV-2 ; SciAdv r-articles ; Spike Glycoprotein, Coronavirus - chemistry</subject><ispartof>Science advances, 2021-01, Vol.7 (1)</ispartof><rights>Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. 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The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>33277323</pmid><doi>10.1126/sciadv.abe5575</doi><orcidid>https://orcid.org/0000-0002-7164-8694</orcidid><orcidid>https://orcid.org/0000-0001-8787-3987</orcidid><orcidid>https://orcid.org/0000-0002-1954-0731</orcidid><orcidid>https://orcid.org/0000-0003-4277-2570</orcidid><orcidid>https://orcid.org/0000-0002-2161-1359</orcidid><orcidid>https://orcid.org/0000-0002-8658-9009</orcidid><orcidid>https://orcid.org/0000-0002-9523-0030</orcidid><orcidid>https://orcid.org/0000-0001-9479-9893</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiotensin-Converting Enzyme 2 - chemistry Animals Coronavirus Cryoelectron Microscopy Enzyme-Linked Immunosorbent Assay Humans Image Processing, Computer-Assisted Ligands Mice Mice, Inbred BALB C Mutation Peptides - chemistry Polysaccharides Principal Component Analysis Protein Binding Protein Domains SARS-CoV-2 SciAdv r-articles Spike Glycoprotein, Coronavirus - chemistry |
| title | Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM |
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