title: Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
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.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Jason S
authors: JS
authors: McLellan
authors: Marie
authors: M
authors: Pancera
authors: Chris
authors: C
authors: Carrico
authors: Jason
authors: J
authors: Gorman
authors: Jean-Philippe
authors: JP
authors: Julien
authors: Reza
authors: R
authors: Khayat
authors: Robert
authors: R
authors: Louder
authors: Robert
authors: R
authors: Pejchal
authors: Mallika
authors: M
authors: Sastry
authors: Kaifan
authors: K
authors: Dai
authors: Sijy
authors: S
authors: O'Dell
authors: Nikita
authors: N
authors: Patel
authors: Syed
authors: S
authors: Shahzad-ul-Hussan
authors: Yongping
authors: Y
authors: Yang
authors: Baoshan
authors: B
authors: Zhang
authors: Tongqing
authors: T
authors: Zhou
authors: Jiang
authors: J
authors: Zhu
authors: Jeffrey C
authors: JC
authors: Boyington
authors: Gwo-Yu
authors: GY
authors: Chuang
authors: Devan
authors: D
authors: Diwanji
authors: Ivelin
authors: I
authors: Georgiev
authors: Young Do
authors: YD
authors: Kwon
authors: Doyung
authors: D
authors: Lee
authors: Mark K
authors: MK
authors: Louder
authors: Stephanie
authors: S
authors: Moquin
authors: Stephen D
authors: SD
authors: Schmidt
authors: Zhi-Yong
authors: ZY
authors: Yang
authors: Mattia
authors: M
authors: Bonsignori
authors: John A
authors: JA
authors: Crump
authors: Saidi H
authors: SH
authors: Kapiga
authors: Noel E
authors: NE
authors: Sam
authors: Barton F
authors: BF
authors: Haynes
authors: Dennis R
authors: DR
authors: Burton
authors: Wayne C
authors: WC
authors: Koff
authors: Laura M
authors: LM
authors: Walker
authors: Sanjay
authors: S
authors: Phogat
authors: Richard
authors: R
authors: Wyatt
authors: Jared
authors: J
authors: Orwenyo
authors: Lai-Xi
authors: LX
authors: Wang
authors: James
authors: J
authors: Arthos
authors: Carole A
authors: CA
authors: Bewley
authors: John R
authors: JR
authors: Mascola
authors: Gary J
authors: GJ
authors: Nabel
authors: William R
authors: WR
authors: Schief
authors: Andrew B
authors: AB
authors: Ward
authors: Ian A
authors: IA
authors: Wilson
authors: Peter D
authors: PD
authors: Kwong
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000276:immunology; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000276:immunology; D001666:Binding Sites, Antibody / Q000276:immunology; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006020:Glycopeptides / Q000737:chemistry / Q000276:immunology; D006031:Glycosylation; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology*; D006860:Hydrogen Bonding; D057131:Immune Evasion; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000936:Antigen-Antibody Complex; D000939:Epitopes; D006020:Glycopeptides; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011134:Polysaccharides