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-Structure paper
タイトル | Structure and inhibition of SARS-CoV-2 spike refolding in membranes. |
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ジャーナル・号・ページ | Science, Vol. 385, Issue 6710, Page 757-765, Year 2024 |
掲載日 | 2024年8月16日 |
著者 | Michael W Grunst / Zhuan Qin / Esteban Dodero-Rojas / Shilei Ding / Jérémie Prévost / Yaozong Chen / Yanping Hu / Marzena Pazgier / Shenping Wu / Xuping Xie / Andrés Finzi / José N Onuchic / Paul C Whitford / Walther Mothes / Wenwei Li / |
PubMed 要旨 | The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme 2 (ACE2) and drives virus-host membrane fusion through refolding of its ...The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme 2 (ACE2) and drives virus-host membrane fusion through refolding of its S2 domain. Whereas the S1 domain contains high sequence variability, the S2 domain is conserved and is a promising pan-betacoronavirus vaccine target. We applied cryo-electron tomography to capture intermediates of S2 refolding and understand inhibition by antibodies to the S2 stem-helix. Subtomogram averaging revealed ACE2 dimers cross-linking spikes before transitioning into S2 intermediates, which were captured at various stages of refolding. Pan-betacoronavirus neutralizing antibodies targeting the S2 stem-helix bound to and inhibited refolding of spike prehairpin intermediates. Combined with molecular dynamics simulations, these structures elucidate the process of SARS-CoV-2 entry and reveal how pan-betacoronavirus S2-targeting antibodies neutralize infectivity by arresting prehairpin intermediates. |
リンク | Science / PubMed:39146425 / PubMed Central |
手法 | EM (サブトモグラム平均) |
解像度 | 18.0 - 24.0 Å |
構造データ | EMDB-42857: Prefusion SARS-CoV-2 Spike bound to ACE2 dimers in membranes EMDB-42859: Prehairpin intermediate of SARS-CoV-2 Spike in membrane EMDB-42865: Post-fusion SARS-CoV-2 Spike in membrane EMDB-42875: ACE2 dimer bound to one RBD in membrane EMDB-42876: ACE2 dimer bound to two RBD in membrane EMDB-42877: ACE2 monomer bound to one RBD in membrane |
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