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

EO Saphire, PWHI Parren, R Pantophlet, MB Zwick… - science, 2001 - science.org
science, 2001science.org
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 …
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.
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