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Conformational flexibility and structural variability of SARS-CoV2 S protein
Spike (S) glycoprotein of SARS-CoV2 exists chiefly in two conformations, open and closed. Most previous structural studies on S protein have been conducted at pH 8.0, but knowledge of the conformational propensities under both physiological and endosomal pH conditions is important to inform vaccine...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086150/ https://www.ncbi.nlm.nih.gov/pubmed/33932324 http://dx.doi.org/10.1016/j.str.2021.04.006 |
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author | Pramanick, Ishika Sengupta, Nayanika Mishra, Suman Pandey, Suman Girish, Nidhi Das, Alakta Dutta, Somnath |
author_facet | Pramanick, Ishika Sengupta, Nayanika Mishra, Suman Pandey, Suman Girish, Nidhi Das, Alakta Dutta, Somnath |
author_sort | Pramanick, Ishika |
collection | PubMed |
description | Spike (S) glycoprotein of SARS-CoV2 exists chiefly in two conformations, open and closed. Most previous structural studies on S protein have been conducted at pH 8.0, but knowledge of the conformational propensities under both physiological and endosomal pH conditions is important to inform vaccine development. Our current study employed single-particle cryoelectron microscopy to visualize multiple states of open and closed conformations of S protein at physiological pH 7.4 and near-physiological pH 6.5 and pH 8.0. Propensities of open and closed conformations were found to differ with pH changes, whereby around 68% of S protein exists in open conformation at pH 7.4. Furthermore, we noticed a continuous movement in the N-terminal domain, receptor-binding domain (RBD), S2 domain, and stalk domain of S protein conformations at various pH values. Several key residues involving RBD-neutralizing epitopes are differentially exposed in each conformation. This study will assist in developing novel therapeutic measures against SARS-CoV2. |
format | Online Article Text |
id | pubmed-8086150 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80861502021-05-03 Conformational flexibility and structural variability of SARS-CoV2 S protein Pramanick, Ishika Sengupta, Nayanika Mishra, Suman Pandey, Suman Girish, Nidhi Das, Alakta Dutta, Somnath Structure Article Spike (S) glycoprotein of SARS-CoV2 exists chiefly in two conformations, open and closed. Most previous structural studies on S protein have been conducted at pH 8.0, but knowledge of the conformational propensities under both physiological and endosomal pH conditions is important to inform vaccine development. Our current study employed single-particle cryoelectron microscopy to visualize multiple states of open and closed conformations of S protein at physiological pH 7.4 and near-physiological pH 6.5 and pH 8.0. Propensities of open and closed conformations were found to differ with pH changes, whereby around 68% of S protein exists in open conformation at pH 7.4. Furthermore, we noticed a continuous movement in the N-terminal domain, receptor-binding domain (RBD), S2 domain, and stalk domain of S protein conformations at various pH values. Several key residues involving RBD-neutralizing epitopes are differentially exposed in each conformation. This study will assist in developing novel therapeutic measures against SARS-CoV2. Elsevier Ltd. 2021-08-05 2021-04-30 /pmc/articles/PMC8086150/ /pubmed/33932324 http://dx.doi.org/10.1016/j.str.2021.04.006 Text en © 2021 Elsevier Ltd. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Pramanick, Ishika Sengupta, Nayanika Mishra, Suman Pandey, Suman Girish, Nidhi Das, Alakta Dutta, Somnath Conformational flexibility and structural variability of SARS-CoV2 S protein |
title | Conformational flexibility and structural variability of SARS-CoV2 S protein |
title_full | Conformational flexibility and structural variability of SARS-CoV2 S protein |
title_fullStr | Conformational flexibility and structural variability of SARS-CoV2 S protein |
title_full_unstemmed | Conformational flexibility and structural variability of SARS-CoV2 S protein |
title_short | Conformational flexibility and structural variability of SARS-CoV2 S protein |
title_sort | conformational flexibility and structural variability of sars-cov2 s protein |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086150/ https://www.ncbi.nlm.nih.gov/pubmed/33932324 http://dx.doi.org/10.1016/j.str.2021.04.006 |
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