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PDBsum entry 7kms
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Hydrolase/viral protein
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PDB id
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7kms
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References listed in PDB file
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Key reference
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Title
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Cryo-Em structures of sars-Cov-2 spike without and with ace2 reveal a ph-Dependent switch to mediate endosomal positioning of receptor-Binding domains.
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Authors
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T.Zhou,
Y.Tsybovsky,
J.Gorman,
M.Rapp,
G.Cerutti,
G.Y.Chuang,
P.S.Katsamba,
J.M.Sampson,
A.Schön,
J.Bimela,
J.C.Boyington,
A.Nazzari,
A.S.Olia,
W.Shi,
M.Sastry,
T.Stephens,
J.Stuckey,
I.T.Teng,
P.Wang,
S.Wang,
B.Zhang,
R.A.Friesner,
D.D.Ho,
J.R.Mascola,
L.Shapiro,
P.D.Kwong.
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Ref.
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Cell Host Microbe, 2020,
28,
867.
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PubMed id
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Abstract
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The SARS-CoV-2 spike employs mobile receptor-binding domains (RBDs) to engage
the human ACE2 receptor and to facilitate virus entry, which can occur through
low-pH-endosomal pathways. To understand how ACE2 binding and low pH affect
spike conformation, we determined cryo-electron microscopy structures-at
serological and endosomal pH-delineating spike recognition of up to three ACE2
molecules. RBDs freely adopted "up" conformations required for ACE2
interaction, primarily through RBD movement combined with smaller alterations in
neighboring domains. In the absence of ACE2, single-RBD-up conformations
dominated at pH 5.5, resolving into a solitary all-down conformation at lower
pH. Notably, a pH-dependent refolding region (residues 824-858) at the
spike-interdomain interface displayed dramatic structural rearrangements and
mediated RBD positioning through coordinated movements of the entire trimer
apex. These structures provide a foundation for understanding prefusion-spike
mechanics governing endosomal entry; we suggest that the low pH all-down
conformation potentially facilitates immune evasion from RBD-up binding antibody.
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