Conformational flexibility and structural variability of SARS-CoV2 S protein.
3D reconstruction
S-head
TEM
cryo-EM
negative staining
pH-dependent
single particle
solvent accessibility
spike homotrimer
stalk domain
Journal
Structure (London, England : 1993)
ISSN: 1878-4186
Titre abrégé: Structure
Pays: United States
ID NLM: 101087697
Informations de publication
Date de publication:
05 08 2021
05 08 2021
Historique:
received:
07
12
2020
revised:
22
02
2021
accepted:
12
04
2021
pubmed:
2
5
2021
medline:
12
1
2022
entrez:
1
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33932324
pii: S0969-2126(21)00122-2
doi: 10.1016/j.str.2021.04.006
pmc: PMC8086150
pii:
doi:
Substances chimiques
Spike Glycoprotein, Coronavirus
0
spike protein, SARS-CoV-2
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
834-845.e5Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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