Science. 2001 Aug 10;293(5532):1155-9.

Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design.

Saphire EO, Parren PW, Pantophlet R, Zwick MB, Morris GM, Rudd PM, Dwek RA, Stanfield RL, Burton DR, Wilson IA.

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Department of Molecular Biology, Department of Immunology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Abstract

We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity.

PMID:: 11498595; [PubMed - indexed for MEDLINE]

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Structures reported by this article

Crystal Structure Of The Intact Human Igg B12 With Broad And Potent Activity Against Primary Hiv-1 Isolates: A Template For Hiv Vaccine Design

PDB: 1HZH

Source: Homo sapiens

Method: X-Ray Diffraction

Resolution: 2.7 Å

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