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

Publication ,  Journal Article
McLellan, 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 ...
Published in: Nature
November 23, 2011

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.

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Published In

Nature

DOI

EISSN

1476-4687

Publication Date

November 23, 2011

Volume

480

Issue

7377

Start / End Page

336 / 343

Location

England

Related Subject Headings

  • Protein Structure, Tertiary
  • Protein Structure, Quaternary
  • Polysaccharides
  • Molecular Sequence Data
  • Models, Molecular
  • Immune Evasion
  • Hydrogen Bonding
  • HIV-1
  • HIV Envelope Protein gp120
  • HIV Antibodies
 

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McLellan, J. S., Pancera, M., Carrico, C., Gorman, J., Julien, J.-P., Khayat, R., … Kwong, P. D. (2011). Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature, 480(7377), 336–343. https://doi.org/10.1038/nature10696
McLellan, Jason S., Marie Pancera, Chris Carrico, Jason Gorman, Jean-Philippe Julien, Reza Khayat, Robert Louder, et al. “Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.Nature 480, no. 7377 (November 23, 2011): 336–43. https://doi.org/10.1038/nature10696.
McLellan JS, Pancera M, Carrico C, Gorman J, Julien J-P, Khayat R, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011 Nov 23;480(7377):336–43.
McLellan, Jason S., et al. “Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.Nature, vol. 480, no. 7377, Nov. 2011, pp. 336–43. Pubmed, doi:10.1038/nature10696.
McLellan 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 YD, 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 R, Orwenyo J, Wang L-X, Arthos J, Bewley CA, Mascola JR, Nabel GJ, Schief WR, Ward AB, Wilson IA, Kwong PD. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011 Nov 23;480(7377):336–343.
Journal cover image

Published In

Nature

DOI

EISSN

1476-4687

Publication Date

November 23, 2011

Volume

480

Issue

7377

Start / End Page

336 / 343

Location

England

Related Subject Headings

  • Protein Structure, Tertiary
  • Protein Structure, Quaternary
  • Polysaccharides
  • Molecular Sequence Data
  • Models, Molecular
  • Immune Evasion
  • Hydrogen Bonding
  • HIV-1
  • HIV Envelope Protein gp120
  • HIV Antibodies