Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design
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- 10 August 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 293 (5532) , 1155-1159
- https://doi.org/10.1126/science.1061692
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.Keywords
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