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2cmr

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==Overview==
==Overview==
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Elicitation of potent and broadly neutralizing antibodies is an important, goal in designing an effective human immunodeficiency virus-1 (HIV-1), vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and, structurally conserved target for therapeutics. Here we report the, 2.0-A-resolution crystal structure of the complex between the, antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and, 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend, on residues in the D5 CDR H2 loop protruding into the conserved gp41, hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41, residues. Kinetic analysis of D5 mutants with perturbed D5-gp41, interactions suggests that D5 persistence at the fusion intermediate is, crucial for neutralization. Thus, our data validate the gp41 N-peptide, trimer fusion intermediate as a target for neutralizing antibodies and, provide a template for identification of more potent and broadly, neutralizing molecules.
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Elicitation of potent and broadly neutralizing antibodies is an important goal in designing an effective human immunodeficiency virus-1 (HIV-1) vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and structurally conserved target for therapeutics. Here we report the 2.0-A-resolution crystal structure of the complex between the antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend on residues in the D5 CDR H2 loop protruding into the conserved gp41 hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41 residues. Kinetic analysis of D5 mutants with perturbed D5-gp41 interactions suggests that D5 persistence at the fusion intermediate is crucial for neutralization. Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules.
==About this Structure==
==About this Structure==
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[[Category: Carfi, A.]]
[[Category: Carfi, A.]]
[[Category: Geleziunas, R.]]
[[Category: Geleziunas, R.]]
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[[Category: Giovine, P.Di.]]
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[[Category: Giovine, P Di.]]
[[Category: Hrin, R.]]
[[Category: Hrin, R.]]
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[[Category: Luftig, M.A.]]
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[[Category: Luftig, M A.]]
[[Category: Mattu, M.]]
[[Category: Mattu, M.]]
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[[Category: Miller, M.D.]]
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[[Category: Miller, M D.]]
[[Category: Pessi, A.]]
[[Category: Pessi, A.]]
[[Category: GOL]]
[[Category: GOL]]
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[[Category: transmembrane]]
[[Category: transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 10:37:02 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:50:22 2008''

Revision as of 14:50, 21 February 2008

Image:2cmr.jpg

2cmr, resolution 2.00Å

Drag the structure with the mouse to rotate

CRYSTAL STRUCTURE OF THE HIV-1 NEUTRALIZING ANTIBODY D5 FAB BOUND TO THE GP41 INNER-CORE MIMETIC 5-HELIX

Overview

Elicitation of potent and broadly neutralizing antibodies is an important goal in designing an effective human immunodeficiency virus-1 (HIV-1) vaccine. The HIV-1 gp41 inner-core trimer represents a functionally and structurally conserved target for therapeutics. Here we report the 2.0-A-resolution crystal structure of the complex between the antigen-binding fragment of D5, an HIV-1 cross-neutralizing antibody, and 5-helix, a gp41 inner-core mimetic. Both binding and neutralization depend on residues in the D5 CDR H2 loop protruding into the conserved gp41 hydrophobic pocket, as well as a large pocket in D5 surrounding core gp41 residues. Kinetic analysis of D5 mutants with perturbed D5-gp41 interactions suggests that D5 persistence at the fusion intermediate is crucial for neutralization. Thus, our data validate the gp41 N-peptide trimer fusion intermediate as a target for neutralizing antibodies and provide a template for identification of more potent and broadly neutralizing molecules.

About this Structure

2CMR is a Single protein structure of sequence from Homo sapiens and Human immunodeficiency virus 1 with as ligand. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structural basis for HIV-1 neutralization by a gp41 fusion intermediate-directed antibody., Luftig MA, Mattu M, Di Giovine P, Geleziunas R, Hrin R, Barbato G, Bianchi E, Miller MD, Pessi A, Carfi A, Nat Struct Mol Biol. 2006 Aug;13(8):740-7. Epub 2006 Jul 23. PMID:16862157

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