Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.

TitleStructure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
Publication TypeJournal Article
Year of Publication2011
AuthorsMcLellan JS, Pancera M, Carrico C, Gorman J, Julien J-P, Khayat R, Louder R, Pejchal R, Sastry M, Dai K, O'Dell S, Patel N, Shahzad-ul-Hussan S, Yang Y, Zhang B, Zhou T, Zhu J, Boyington JC, Chuang G-Y, Diwanji D, Georgiev I, Kwon Y D, Lee D, Louder MK, Moquin S, Schmidt SD, Yang Z-Y, Bonsignori M, Crump JA, Kapiga SH, Sam NE, Haynes BF, Burton DR, Koff WC, Walker LM, Phogat S, Wyatt RT, Orwenyo J, Wang L-X, Arthos J, Bewley CA, Mascola JR, Nabel GJ, Schief WR, Ward AB, Wilson IA, Kwong PD
JournalNature
Volume480
Issue7377
Pagination336-43
Date Published2011 Dec 15
ISSN1476-4687
KeywordsAIDS Vaccines, Amino Acid Motifs, Amino Acid Sequence, Antibodies, Neutralizing, Antibody Affinity, Antibody Specificity, Antigen-Antibody Complex, Binding Sites, Antibody, Conserved Sequence, Crystallography, X-Ray, Epitopes, Glycopeptides, Glycosylation, HIV Antibodies, HIV Envelope Protein gp120, HIV-1, Hydrogen Bonding, Immune Evasion, Models, Molecular, Molecular Sequence Data, Polysaccharides, Protein Structure, Quaternary, Protein Structure, Tertiary
Abstract

Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.

DOI10.1038/nature10696
Alternate JournalNature
PubMed ID22113616