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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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PDB id:
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Virus/immune system
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Title:
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Cryo-em structure of chikungunya virus in complex with mab chk-263 igg (subregion around icosahedral 2-fold vertex)
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Structure:
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E1 glycoprotein. Chain: a, c, g, e, k, i, i, g, e, w, u, y, s, c, a, q, o, m. E2 glycoprotein. Chain: b, d, h, f, l, j, j, h, f, x, v, z, t, d, b, r, p, n. Fab heavy chain. Chain: q, k, m, o. Fab light chain. Chain: r, l, n, p. Capsid protein.
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Source:
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Chikungunya virus. Chikv. Organism_taxid: 37124. Mus musculus. Organism_taxid: 10090. Organism_taxid: 37124
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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,B.Shu,M.S.Diamond,S.M.Lok
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Key ref:
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Q.F.Zhou
et al.
(2020).
Structural basis of Chikungunya virus inhibition by monoclonal antibodies.
Proc Natl Acad Sci U S A,
117,
27637-27645.
PubMed id:
DOI:
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Date:
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27-Aug-20
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Release date:
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04-Nov-20
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Headers
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References
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Q8JUX5
(POLS_CHIKS) -
Structural polyprotein from Chikungunya virus (strain S27-African prototype)
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Seq:
Struc:
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1248 a.a.
439 a.a.*
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Q8JUX5
(POLS_CHIKS) -
Structural polyprotein from Chikungunya virus (strain S27-African prototype)
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Seq:
Struc:
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1248 a.a.
419 a.a.*
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No UniProt id for this chain
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Enzyme class:
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Chains A, B, C, D, G, H, E, F, K, L, I, J, i, j, g, h, e, f, s, W, X, U, V, Y, Z, S, T, c, d, a, b, Q, R, O, P, M, N, t:
E.C.3.4.21.90
- togavirin.
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Reaction:
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Autocatalytic release of the core protein from the N-terminus of the togavirus structural protein by hydrolysis of a Trp-|-Ser bond.
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DOI no:
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Proc Natl Acad Sci U S A
117:27637-27645
(2020)
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PubMed id:
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Structural basis of Chikungunya virus inhibition by monoclonal antibodies.
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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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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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