Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants
Abstract The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, “in-situ” high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S..
Medienart: |
Preprint |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
bioRxiv.org - (2023) vom: 27. Dez. Zur Gesamtaufnahme - year:2023 |
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Sprache: |
Englisch |
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Beteiligte Personen: |
Ke, Zunlong [VerfasserIn] |
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Links: |
Volltext [kostenfrei] |
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Themen: |
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doi: |
10.1101/2023.12.21.572824 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
XBI041965612 |
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520 | |a Abstract The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins that are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S from SARS-CoV-2 variants has revealed this structural adaptation at high-resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology. Here, we characterized B.1, Alpha, Beta, Gamma, Delta, Kappa, and Mu variants by cryo-electron microscopy and tomography, assessing S cleavage, virion morphology, S incorporation, “in-situ” high-resolution S structures and the range of S conformational states. We found no evidence for adaptive changes in virion morphology, but describe multiple different positions in the S protein where amino acid changes alter local protein structure. Considered together, our data is consistent with a model where amino acid changes at multiple positions from the top to the base of the spike cause structural changes that can modulate the conformational dynamics of S. | ||
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700 | 1 | |a Peacock, Thomas P. |0 (orcid)0000-0001-7077-2928 |4 aut | |
700 | 1 | |a Brown, Jonathan C. |0 (orcid)0000-0001-6849-3962 |4 aut | |
700 | 1 | |a Sheppard, Carol M. |0 (orcid)0000-0002-3285-3804 |4 aut | |
700 | 1 | |a Croll, Tristan I. |0 (orcid)0000-0002-3514-8377 |4 aut | |
700 | 1 | |a Kotecha, Abhay |0 (orcid)0000-0002-4480-5439 |4 aut | |
700 | 1 | |a Goldhill, Daniel H. |0 (orcid)0000-0003-4597-5963 |4 aut | |
700 | 1 | |a Barclay, Wendy S. |0 (orcid)0000-0002-3948-0895 |4 aut | |
700 | 1 | |a Briggs, John A.G. |0 (orcid)0000-0003-3990-6910 |4 aut | |
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