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.
Type
Journal articleSubject
AIDS VaccinesAmino 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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https://hdl.handle.net/10161/13795Published Version (Please cite this version)
10.1038/nature10696Publication Info
McLellan, JS; Pancera, M; Carrico, C; Gorman, J; Julien, JP; Khayat, R; ... Kwong,
PD (2011). Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature, 480(7377). pp. 336-343. 10.1038/nature10696. Retrieved from https://hdl.handle.net/10161/13795.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Mattia Bonsignori
Associate Professor in Medicine
HIV vaccine development Study of B-cell immune responses in HIV positive individuals
Determination of correlates of protective immunity to HIV Induction of broadly neutralizing
antibodies to HIV Development of multiplex functional assays for the evaluation at
a single-cell level of B-cell responses to vaccinations, infections and in vitro stimulation
Epidemiology and characterization of bacterial resistance determinants (past) </do
This author no longer has a Scholars@Duke profile, so the information shown here reflects
their Duke status at the time this item was deposited.
John Andrew Crump
Adjunct Professor in the Department of Medicine
I am based in northern Tanzania where I am Site Leader for Duke University’s
collaborative research program based at Kilimanjaro Christian Medical Centre and Director
of Tanzania Operations for the Duke Global Health Institute. I oversee the design
and implementation of research studies on infectious diseases, particularly febrile
illness, invasive bacterial disease, HIV-associated opportunistic infections, clinical
trials of antiretroviral therapy and prevention of mother-to-child tr
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
Barton F. Haynes, M.D. is the Frederic M. Hanes Professor of Medicine and Immunology,
and Director of the Duke Human Vaccine Institute. Prior to leading the DHVI, Dr. Haynes
served as Chief of the Division of Rheumatology, Allergy and Clinical Immunology,
and later as Chair of the Department of Medicine. As Director of the Duke Human Vaccine
Institute, Bart Haynes is leading a team of investigators working on vaccines for
emerging infections, including tuberculosis, pandemic influenza, emergi
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