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PDBsum entry 1tji
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Viral protein/immune system
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PDB id
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1tji
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Contents |
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214 a.a.
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237 a.a.
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15 a.a.
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structure and mechanistic analysis of the anti-Human immunodeficiency virus type 1 antibody 2f5 in complex with its gp41 epitope.
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Authors
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G.Ofek,
M.Tang,
A.Sambor,
H.Katinger,
J.R.Mascola,
R.Wyatt,
P.D.Kwong.
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Ref.
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J Virol, 2004,
78,
10724-10737.
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PubMed id
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Abstract
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The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein
of human immunodeficiency virus type 1 (HIV-1) is the target of three of the
five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have
determined crystal structures of the antigen-binding fragment for one of these
antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41
membrane-proximal region, at 2.0-, 2.1-, and 2.2-A resolutions, respectively.
The structures reveal an extended gp41 conformation, which stretches over 30 A
in length. Contacts are made with five complementarity-determining regions of
the antibody as well as with nonpolymorphic regions. Only one exclusive charged
face of the gp41 epitope is bound by 2F5, while the nonbound face, which is
hydrophobic, may be hidden due to occlusion by other portions of the ectodomain.
The structures reveal that the 2F5 antibody is uniquely built to bind to an
epitope that is proximal to a membrane surface and in a manner mostly unaffected
by large-scale steric hindrance. Biochemical studies with proteoliposomes
confirm the importance of lipid membrane and hydrophobic context in the binding
of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody
that recognizes the membrane-proximal region of gp41. Based on these structural
and biochemical results, immunization strategies for eliciting 2F5- and
4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed.
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