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Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics

التفاصيل البيبلوغرافية
العنوان: Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics
المؤلفون: Sean M Braet, Theresa SC Buckley, Varun Venkatakrishnan, Kim-Marie A Dam, Pamela J Bjorkman, Ganesh S Anand
المصدر: eLife, Vol 12 (2023)
بيانات النشر: eLife Sciences Publications Ltd, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: mass spectrometry, HDXMS, conformational dynamics, allostery, protein-protein interactions, SARS-CoV-2, Medicine, Science, Biology (General), QH301-705.5
الوصف: 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/82584; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.82584
URL الوصول: https://doaj.org/article/e132c898884c4543b6bf006d6de5b0b7
رقم الأكسشن: edsdoj.132c898884c4543b6bf006d6de5b0b7
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.82584