D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction.
Cell Rep
; 34(2): 108630, 2021 01 12.
Article
in English
| MEDLINE | ID: covidwho-987231
ABSTRACT
The severe acute respiratory coronavirus 2 (SARS-CoV-2) spike (S) protein is the target of vaccine design efforts to end the coronavirus disease 2019 (COVID-19) pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic and are now the dominant form worldwide. Here, we explore S conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryoelectron microscopy (cryo-EM) structures reveal altered receptor binding domain (RBD) disposition; antigenicity and proteolysis experiments reveal structural changes and enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage alters the up/down ratio of the RBDs in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, which harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 S conformational landscape and allostery and have implications for vaccine design.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Peptide Hydrolases
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Topics:
Vaccines
/
Variants
Limits:
Humans
Language:
English
Journal:
Cell Rep
Year:
2021
Document Type:
Article
Affiliation country:
J.celrep.2020.108630
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