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PDBsum entry 7cw3
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Virus/immune system
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PDB id
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7cw3
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Contents |
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(+ 12 more)
439 a.a.*
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(+ 12 more)
419 a.a.*
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216 a.a.*
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213 a.a.*
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151 a.a.*
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* C-alpha coords only
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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 basis of chikungunya virus inhibition by monoclonal antibodies.
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Authors
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Q.F.Zhou,
J.M.Fox,
J.T.Earnest,
T.S.Ng,
A.S.Kim,
G.Fibriansah,
V.A.Kostyuchenko,
J.Shi,
B.Shu,
M.S.Diamond,
S.M.Lok.
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Ref.
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Proc Natl Acad Sci U S A, 2020,
117,
27637-27645.
[DOI no: ]
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PubMed id
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Abstract
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Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute
and chronic debilitating arthritis. Here, we describe the functional and
structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and
CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro
studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral
infection. CHK-124 aggregates virus particles and blocks attachment. Also, due
to antibody-induced virus aggregation, fusion with endosomes and egress are
inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus
attachment and fusion. To determine the structural basis of neutralization, we
generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes
at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the
Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that
spans across E1 and E2 and locks the heterodimer together, likely preventing
structural rearrangements required for fusion. These results provide structural
insight as to how neutralizing antibody engagement of CHIKV inhibits different
stages of the viral life cycle, which could inform vaccine and therapeutic
design.
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Headers
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