Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes
© 2023 Zhang et al..
SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 9 vom: 04. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Xixi [VerfasserIn] |
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| Links: |
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| Themen: |
Disulfides |
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| Anmerkungen: |
Date Completed 06.07.2023 Date Revised 18.08.2023 published: Electronic-Print PDB: 5X58, 7XTZ, 7XU2, 7XU3, 6XM5, 7BBH, 7CN8, 7CN4, 6ZGF, 5X5B, 5XLR, 6ACC, 6ACD, 6CRW, 8H14, 7LM9, 8DW2, 8H0X, 8H0Y, 8H0Z, 8H10, 8H11, 8H12, 8H13, 8H15, 8H16 Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202201796 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359037739 |
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| 100 | 1 | |a Zhang, Xixi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes |
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| 500 | |a Date Revised 18.08.2023 | ||
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Zhang et al. | ||
| 520 | |a SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 7 | |a Disulfides |2 NLM | |
| 700 | 1 | |a Li, Zimu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yutong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jingjing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Banghui |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qiuluan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Lutang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Peiyi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Xiaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Qihong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a He, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Xiong, Xiaoli |e verfasserin |4 aut | |
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