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PDBsum entry 7kec
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Viral protein
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PDB id
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7kec
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References listed in PDB file
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Key reference
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Title
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D614g mutation alters sars-Cov-2 spike conformation and enhances protease cleavage at the s1/s2 junction.
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Authors
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S.M.Gobeil,
K.Janowska,
S.Mcdowell,
K.Mansouri,
R.Parks,
K.Manne,
V.Stalls,
M.F.Kopp,
R.Henderson,
R.J.Edwards,
B.F.Haynes,
P.Acharya.
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Ref.
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Cell Rep, 2021,
34,
108630.
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PubMed id
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Abstract
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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.
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