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TitleConformational flexibility and structural variability of SARS-CoV2 S protein.
Journal, issue, pagesStructure, Vol. 29, Issue 8, Page 834-845.e5, Year 2021
Publish dateAug 5, 2021
AuthorsIshika Pramanick / Nayanika Sengupta / Suman Mishra / Suman Pandey / Nidhi Girish / Alakta Das / Somnath Dutta /
PubMed AbstractSpike (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 ...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.
External linksStructure / PubMed:33932324 / PubMed Central
MethodsEM (single particle)
Resolution3.88 - 5.76 Å
Structure data

EMDB-31092:
SARS-CoV2 Spike Protein structure at pH 6.5 with C1 Symmetry (Class 2)
Method: EM (single particle) / Resolution: 4.75 Å

EMDB-31093:
SARS-CoV2 Spike Protein structure at pH 6.5 with C1 Symmetry (Class 3)
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-31094:
SARS-CoV2 Spike Protein structure at pH 6.5 with C1 Symmetry (Class 4)
Method: EM (single particle) / Resolution: 5.44 Å

EMDB-31095:
SARS-CoV2 Spike Protein structure at pH 6.5 with C1 Symmetry (Class 5)
Method: EM (single particle) / Resolution: 4.53 Å

EMDB-31096:
SARS-CoV2 Spike Protein structure at pH 7.4 with C1 Symmetry (Class 3)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-31097:
SARS-CoV2 Spike Protein structure at pH 7.4 with C1 Symmetry (Class 5)
Method: EM (single particle) / Resolution: 4.16 Å

EMDB-31098:
SARS-CoV2 Spike Protein structure at pH 7.4 with C3 Symmetry
Method: EM (single particle) / Resolution: 3.88 Å

EMDB-31099:
SARS-CoV2 Spike Protein structure at pH 8.0 with C1 Symmetry (Class 1)
Method: EM (single particle) / Resolution: 5.76 Å

EMDB-31100:
SARS-CoV2 Spike Protein structure at pH 7.4 with C1 Symmetry (Class 9)
Method: EM (single particle) / Resolution: 4.34 Å

EMDB-31101:
SARS-CoV2 Spike Protein structure at pH 7.4 with C1 Symmetry (Class 8)
Method: EM (single particle) / Resolution: 4.47 Å

EMDB-31102:
SARS-CoV2 Spike Protein structure at pH 8.0 with C1 Symmetry (Class 2)
Method: EM (single particle) / Resolution: 5.34 Å

Source
  • Severe acute respiratory syndrome coronavirus 2

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