2cmr
From Proteopedia
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==Overview== | ==Overview== | ||
- | Elicitation of potent and broadly neutralizing antibodies is an important | + | 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.]] | ||
- | [[Category: Giovine, P | + | [[Category: Giovine, P Di.]] |
[[Category: Hrin, R.]] | [[Category: Hrin, R.]] | ||
- | [[Category: Luftig, M | + | [[Category: Luftig, M A.]] |
[[Category: Mattu, M.]] | [[Category: Mattu, M.]] | ||
- | [[Category: Miller, M | + | [[Category: Miller, M D.]] |
[[Category: Pessi, A.]] | [[Category: Pessi, A.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: transmembrane]] | [[Category: transmembrane]] | ||
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''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
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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
Page seeded by OCA on Thu Feb 21 16:50:22 2008
Categories: Homo sapiens | Human immunodeficiency virus 1 | Single protein | Barbato, G. | Bianchi, E. | Carfi, A. | Geleziunas, R. | Giovine, P Di. | Hrin, R. | Luftig, M A. | Mattu, M. | Miller, M D. | Pessi, A. | GOL | Aids | Envelope protein | Gp41 | Hiv | Immunoglobulin | Immunoglobulin complex | Immunoglobulin domain | Membrane | Mhc i | Neutralization | Transmembrane