Autor: |
Sean M Braet, Theresa SC Buckley, Varun Venkatakrishnan, Kim-Marie A Dam, Pamela J Bjorkman, Ganesh S Anand |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
eLife, Vol 12 (2023) |
Druh dokumentu: |
article |
ISSN: |
2050-084X |
DOI: |
10.7554/eLife.82584 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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