Publication Date:
2001-08-11
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Saphire, E O -- Parren, P W -- Pantophlet, R -- Zwick, M B -- Morris, G M -- Rudd, P M -- Dwek, R A -- Stanfield, R L -- Burton, D R -- Wilson, I A -- AI33292/AI/NIAID NIH HHS/ -- AI40377/AI/NIAID NIH HHS/ -- GM46192/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2001 Aug 10;293(5532):1155-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉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.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11498595" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines
;
Amino Acid Sequence
;
Antigens, CD4/metabolism
;
Binding Sites
;
Binding Sites, Antibody
;
Complementarity Determining Regions/chemistry
;
Crystallography, X-Ray
;
Epitopes
;
HIV Antibodies/*chemistry/immunology
;
HIV Envelope Protein gp120/chemistry/*immunology/metabolism
;
HIV-1/*immunology
;
Humans
;
Hydrogen Bonding
;
Immunoglobulin G/*chemistry/immunology
;
Models, Molecular
;
Molecular Sequence Data
;
Neutralization Tests
;
Peptide Library
;
Protein Conformation
;
Protein Structure, Tertiary
;
Templates, Genetic
;
Thermodynamics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
