Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
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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.
Amino Acid Motifs
Amino Acid Sequence
Binding Sites, Antibody
HIV Envelope Protein gp120
Molecular Sequence Data
Protein Structure, Quaternary
Protein Structure, Tertiary
Published Version (Please cite this version)10.1038/nature10696
Publication InfoMcLellan, Jason S; Pancera, Marie; Carrico, Chris; Gorman, Jason; Julien, Jean-Philippe; Khayat, Reza; ... Kwong, Peter D (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.
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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
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
Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the enabling technology to make preventive vaccines against these three major infectious diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working to determine why broadly neutralizing antibodies are rarely made in acute HIV infection (AHI), currently a major obstacle in the de
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