Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics
SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. O...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/82584 |
| _version_ | 1797858647010705408 |
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| author | Sean M Braet Theresa SC Buckley Varun Venkatakrishnan Kim-Marie A Dam Pamela J Bjorkman Ganesh S Anand |
| author_facet | Sean M Braet Theresa SC Buckley Varun Venkatakrishnan Kim-Marie A Dam Pamela J Bjorkman Ganesh S Anand |
| author_sort | Sean M Braet |
| collection | DOAJ |
| description | SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development. |
| first_indexed | 2024-04-09T21:16:44Z |
| format | Article |
| id | doaj.art-e132c898884c4543b6bf006d6de5b0b7 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T21:16:44Z |
| publishDate | 2023-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e132c898884c4543b6bf006d6de5b0b72023-03-28T08:58:57ZengeLife Sciences Publications LtdeLife2050-084X2023-03-011210.7554/eLife.82584Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamicsSean M Braet0https://orcid.org/0000-0003-3782-2262Theresa SC Buckley1https://orcid.org/0009-0005-2897-9630Varun Venkatakrishnan2Kim-Marie A Dam3Pamela J Bjorkman4https://orcid.org/0000-0002-2277-3990Ganesh S Anand5https://orcid.org/0000-0001-8995-3067Department of Chemistry, Pennsylvania State University, University Park, United StatesDepartment of Chemistry, Pennsylvania State University, University Park, United StatesDepartment of Chemistry, Pennsylvania State University, University Park, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDepartment of Chemistry, Pennsylvania State University, University Park, United States; Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, United States; The Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, United StatesSARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.https://elifesciences.org/articles/82584mass spectrometryHDXMSconformational dynamicsallosteryprotein-protein interactionsSARS-CoV-2 |
| spellingShingle | Sean M Braet Theresa SC Buckley Varun Venkatakrishnan Kim-Marie A Dam Pamela J Bjorkman Ganesh S Anand Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics eLife mass spectrometry HDXMS conformational dynamics allostery protein-protein interactions SARS-CoV-2 |
| title | Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics |
| title_full | Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics |
| title_fullStr | Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics |
| title_full_unstemmed | Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics |
| title_short | Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics |
| title_sort | timeline of changes in spike conformational dynamics in emergent sars cov 2 variants reveal progressive stabilization of trimer stalk with altered ntd dynamics |
| topic | mass spectrometry HDXMS conformational dynamics allostery protein-protein interactions SARS-CoV-2 |
| url | https://elifesciences.org/articles/82584 |
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