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PDBsum entry 5i8c
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Immune system
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PDB id
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5i8c
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References listed in PDB file
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Key reference
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Title
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Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
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Authors
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R.Kong,
K.Xu,
T.Zhou,
P.Acharya,
T.Lemmin,
K.Liu,
G.Ozorowski,
C.Soto,
J.D.Taft,
R.T.Bailer,
E.M.Cale,
L.Chen,
C.W.Choi,
G.Y.Chuang,
N.A.Doria-Rose,
A.Druz,
I.S.Georgiev,
J.Gorman,
J.Huang,
M.G.Joyce,
M.K.Louder,
X.Ma,
K.Mckee,
S.O'Dell,
M.Pancera,
Y.Yang,
S.C.Blanchard,
W.Mothes,
D.R.Burton,
W.C.Koff,
M.Connors,
A.B.Ward,
P.D.Kwong,
J.R.Mascola.
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Ref.
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Science, 2016,
352,
828-833.
[DOI no: ]
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PubMed id
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Abstract
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The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N
terminus of the Env-gp41 subunit, is a critical component of the virus-cell
entry machinery. Here, we report the identification of a neutralizing antibody,
N123-VRC34.01, which targets the fusion peptide and blocks viral entry by
inhibiting conformational changes in gp120 and gp41 subunits of Env required for
entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and
to the full Env trimer, revealed an epitope consisting of the N-terminal eight
residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular
dynamics showed that the N-terminal portion of the fusion peptide can be
solvent-exposed. These results reveal the fusion peptide to be a neutralizing
antibody epitope and thus a target for vaccine design.
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