D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction | Zendy

S. Gobeil | Zendy; Katarzyna Janowska | Zendy; Shana McDowell | Zendy; Katayoun Mansouri | Zendy; Robert Parks | Zendy; Kartik Manne | Zendy; Victoria Stalls | Zendy; Megan Kopp | Zendy; Rory Henderson | Zendy; Robert J. Edwards | Zendy; Barton F. Haynes | Zendy; Priyamvada Acharya | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

D614G Mutation Alters SARS-CoV-2 Spike Conformation and Enhances Protease Cleavage at the S1/S2 Junction

Author(s) -

S. Gobeil,

Katarzyna Janowska,

Shana McDowell,

Katayoun Mansouri,

Robert Parks,

Kartik Manne,

Victoria Stalls,

Megan Kopp,

Rory Henderson,

Robert J. Edwards,

Barton F. Haynes,

Priyamvada Acharya

Publication year - 2020

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2020.108630

Subject(s) - furin , ectodomain , allosteric regulation , cleavage (geology) , coronavirus , biology , proteolysis , protease , mutation , mutant , biogenesis , protein structure , microbiology and biotechnology , virology , chemistry , biochemistry , receptor , enzyme , covid-19 , gene , medicine , disease , pathology , fracture (geology) , infectious disease (medical specialty) , paleontology

The SARS-CoV-2 spike (S) protein is the target of vaccine design efforts to end the 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 spike conformational changes and the effects of the D614G mutation on a soluble S ectodomain construct. Cryo-EM structures reveal altered 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 Receptor Binding Domains (RBD) in the G614 S ectodomain, demonstrating an allosteric effect on RBD positioning triggered by changes in the SD2 region, that harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 spike conformational landscape and allostery, and have implications for vaccine design.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research