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PDBsum entry 4jdv
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Immune system
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PDB id
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4jdv
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Contents |
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227 a.a.
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208 a.a.
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215 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 basis for HIV-1 gp120 recognition by a germ-Line version of a broadly neutralizing antibody.
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Authors
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L.Scharf,
A.P.West,
H.Gao,
T.Lee,
J.F.Scheid,
M.C.Nussenzweig,
P.J.Bjorkman,
R.Diskin.
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Ref.
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Proc Natl Acad Sci U S A, 2013,
110,
6049-6054.
[DOI no: ]
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PubMed id
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Abstract
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Efforts to design an effective antibody-based vaccine against HIV-1 would
benefit from understanding how germ-line B-cell receptors (BCRs) recognize the
HIV-1 gp120/gp41 envelope spike. Potent VRC01-like (PVL) HIV-1 antibodies
derived from the VH1-2*02 germ-line allele target the conserved CD4 binding site
on gp120. A bottleneck for design of immunogens capable of eliciting PVL
antibodies is that VH1-2*02 germ-line BCR interactions with gp120 are
uncharacterized. Here, we report the structure of a VH1-2*02 germ-line antibody
alone and a germ-line heavy-chain/mature light-chain chimeric antibody complexed
with HIV-1 gp120. VH1-2*02 residues make extensive contacts with the gp120 outer
domain, including all PVL signature and CD4 mimicry interactions, but not
critical CDRH3 contacts with the gp120 inner domain and bridging sheet that are
responsible for the improved potency of NIH45-46 over closely related clonal
variants, such as VRC01. Our results provide insight into initial recognition of
HIV-1 by VH1-2*02 germ-line BCRs and may facilitate the design of immunogens
tailored to engage and stimulate broad and potent CD4 binding site antibodies.
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