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PDBsum entry 6pxh
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Immune system/viral protein
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PDB id
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6pxh
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Contents |
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334 a.a.
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213 a.a.
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218 a.a.
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References listed in PDB file
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Key reference
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Title
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Structural definition of a neutralization-Sensitive epitope on the mers-Cov s1-Ntd.
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Authors
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N.Wang,
O.Rosen,
L.Wang,
H.L.Turner,
L.J.Stevens,
K.S.Corbett,
C.A.Bowman,
J.Pallesen,
W.Shi,
Y.Zhang,
K.Leung,
R.N.Kirchdoerfer,
M.M.Becker,
M.R.Denison,
J.D.Chappell,
A.B.Ward,
B.S.Graham,
J.S.Mclellan.
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Ref.
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Cell Rep, 2019,
28,
3395.
[DOI no: ]
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PubMed id
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Abstract
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Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human
population in 2012 and has caused substantial morbidity and mortality. Potently
neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV
spike (S) protein have been characterized, but much less is known about
antibodies targeting non-RBD epitopes. Here, we report the structural and
functional characterization of G2, a neutralizing antibody targeting the
MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex
with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops,
each of which contain a residue mutated in G2-escape variants. Cell-surface
binding studies and in vitro competition experiments demonstrate that G2
strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl
peptidase-4 (DPP4), with the inhibition requiring the native trimeric S
conformation. These results advance our understanding of antibody-mediated
neutralization of coronaviruses and should facilitate the development of
immunotherapeutics and vaccines against MERS-CoV.
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