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

Academic Article
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Overview

related to degree

  • Walker, Laura, Ph.D. in Immunology, Scripps Research 2007 - 2011

authors

  • McLellan, J. S.
  • Pancera, M.
  • Carrico, C.
  • Gorman, J.
  • Julien, J. P.
  • Khayat, R.
  • Louder, R.
  • Pejchal, R.
  • Sastry, M.
  • Dai, K. F.
  • O'Dell, S.
  • Patel, N.
  • Shahzad-ul-Hussan, S.
  • Yang, Y. P.
  • Zhang, B. S.
  • Zhou, T. Q.
  • Zhu, Jiang
  • Boyington, J. C.
  • Chuang, G. Y.
  • Diwanji, D.
  • Georgiev, I.
  • Do Kwon, Y.
  • Lee, D.
  • Louder, M. K.
  • Moquin, S.
  • Schmidt, S. D.
  • Yang, Z. Y.
  • Bonsignori, M.
  • Crump, J. A.
  • Kapiga, S. H.
  • Sam, N. E.
  • Haynes, B. F.
  • Burton, Dennis
  • Koff, W. C.
  • Walker, Laura
  • Phogat, S.
  • Wyatt, Richard
  • Orwenyo, J.
  • Wang, L. X.
  • Arthos, J.
  • Bewley, C. A.
  • Mascola, J. R.
  • Nabel, G. J.
  • Schief, William
  • Ward, Andrew
  • Wilson, Ian
  • Kwong, P. D.

publication date

  • December 2011

journal

  • Nature  Journal

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.

subject areas

  • AIDS 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
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Identity

PubMed Central ID

  • PMC3406929

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature10696

PubMed ID

  • 22113616
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Additional Document Info

start page

  • 336

end page

  • 343

volume

  • 480

issue

  • 7377

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