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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
Nature, Volume 480, No. 7377, Year 2011
Notification
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Description
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. © 2011 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
McLellan, Jason S.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Pancera, Marie
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Carrico, Chris
United States, Seattle
University of Washington
Gorman, Jason
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Julien, Jean Philippe
United States, San Diego
Scripps Research Institute
Khayat, Reza
United States, San Diego
Scripps Research Institute
Louder, Robert
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Pejchal, Robert
United States, San Diego
Scripps Research Institute
Sastry, Mallika
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Dai, Kaifan
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
O'Dell, Sijy J.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Patel, Nikita
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Shahzad-Ul-Hussan, Syed
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
United States, Bethesda
National Institute of Diabetes and Digestive and Kidney Diseases Niddk
Yang, Yongping
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Zhang, Baoshan
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Zhou, Tongqing
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Zhu, Jiang
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Boyington, Jeffrey C.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Chuang, Gwoyu
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Diwanji, Devan
United States, San Diego
Scripps Research Institute
Georgiev, Ivelin S.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Do Kwon, Young
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Lee, Doyung
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Louder, Mark K.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Moquin, Stephanie
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Schmidt, Stephen D.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Yang, Zhi Yong
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Bonsignori, Mattia
United States, Durham
Duke University School of Medicine
Crump, John A.
United States, Durham
Duke University Medical Center
Tanzania, Moshi
Kilimanjaro Christian Medical University College
Kapiga, Saidi Hussein
Tanzania
Kilimanjaro Reproductive Health Program
Sam, Noel E.
Tanzania, Moshi
Kilimanjaro Christian Medical University College
Tanzania
Kilimanjaro Reproductive Health Program
Haynes, Barton F.
United States, Durham
Duke University School of Medicine
Burton, Dennis Raymond
United States, San Diego
Scripps Research Institute
United States, Cambridge
Massachusetts Institute of Technology
Koff, Wayne C.
United States, New York
International Aids Vaccine Initiative
Walker, Laura M.
United States, San Diego
Scripps Research Institute
Phogat, Sanjay Kumar
United States, New York
International Aids Vaccine Initiative
Wyatt, Richard
United States, San Diego
Scripps Research Institute
Orwenyo, Jared
United States, Baltimore
University of Maryland School of Medicine
Wang, Laixi
United States, Baltimore
University of Maryland School of Medicine
Arthos, James A.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Bewley, Carole A.
United States, Bethesda
National Institute of Diabetes and Digestive and Kidney Diseases Niddk
Mascola, John R.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Nabel, Gary J.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Schief, William R.
United States, Seattle
University of Washington
United States, San Diego
Scripps Research Institute
Ward, Andrew B.
United States, San Diego
Scripps Research Institute
Wilson, Ian A.
United States, San Diego
Scripps Research Institute
Kwong, Peter D.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Statistics
Citations: 828
Authors: 47
Affiliations: 11
Identifiers
Doi:
10.1038/nature10696
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Infectious Diseases