The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel
Abstract
The region consisting of the first and second variable regions (V1V2) of gp120 plays vital roles in the functioning of the HIV-1 envelope (Env). V1V2, which harbors multiple glycans and is highly sequence diverse, is located at the Env apex and stabilizes the trimeric gp120 spike on the virion surface. It shields V3 and the coreceptor binding sites in the prefusion state and exposes them upon CD4 binding. Data from the RV144 human HIV-1 vaccine trial suggested that antibody responses targeting the V1V2 region inversely correlated with the risk of infection; thus, understanding the antigenic structure of V1V2 can contribute to vaccine design. We have determined a crystal structure of a V1V2 scaffold molecule (V1V2ZM109-1FD6) in complex with 830A, a human monoclonal antibody that recognizes a V1V2 epitope overlapping the integrin-binding motif in V2. The structure revealed that V1V2 assumes a five-stranded beta barrel structure with the region of the integrin-binding site (amino acids [aa] 179 to 181) included in a “kink” followed by an extra beta strand. The complete barrel structure naturally presents the glycans on its outer surface and packs into its core conserved hydrophobic residues, including the Ile at position 181 which was highly correlated with vaccinemore »
- Authors:
-
- NYU School of Medicine, NY (United States)
- NYU School of Medicine, NY (United States); Veterans Affairs New York Harbor Healthcare System, New York, NY (United States)
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of Health; National Cancer Inst.; National Inst. of General Medical Sciences
- OSTI Identifier:
- 1213733
- Grant/Contract Number:
- AC02-06CH11357; AI100151; AI082274; AI084119; HL059725; Y1-CO-1020; Y1-GM-1104
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Virology
- Additional Journal Information:
- Journal Volume: 89; Journal Issue: 15; Journal ID: ISSN 0022-538X
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Pan, Ruimin, Gorny, Miroslaw K., Zolla-Pazner, Susan, and Kong, Xiang-Peng. The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel. United States: N. p., 2015.
Web. doi:10.1128/JVI.00754-15.
Pan, Ruimin, Gorny, Miroslaw K., Zolla-Pazner, Susan, & Kong, Xiang-Peng. The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel. United States. https://doi.org/10.1128/JVI.00754-15
Pan, Ruimin, Gorny, Miroslaw K., Zolla-Pazner, Susan, and Kong, Xiang-Peng. Wed .
"The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel". United States. https://doi.org/10.1128/JVI.00754-15. https://www.osti.gov/servlets/purl/1213733.
@article{osti_1213733,
title = {The V1V2 Region of HIV-1 gp120 Forms a Five-Stranded Beta Barrel},
author = {Pan, Ruimin and Gorny, Miroslaw K. and Zolla-Pazner, Susan and Kong, Xiang-Peng},
abstractNote = {The region consisting of the first and second variable regions (V1V2) of gp120 plays vital roles in the functioning of the HIV-1 envelope (Env). V1V2, which harbors multiple glycans and is highly sequence diverse, is located at the Env apex and stabilizes the trimeric gp120 spike on the virion surface. It shields V3 and the coreceptor binding sites in the prefusion state and exposes them upon CD4 binding. Data from the RV144 human HIV-1 vaccine trial suggested that antibody responses targeting the V1V2 region inversely correlated with the risk of infection; thus, understanding the antigenic structure of V1V2 can contribute to vaccine design. We have determined a crystal structure of a V1V2 scaffold molecule (V1V2ZM109-1FD6) in complex with 830A, a human monoclonal antibody that recognizes a V1V2 epitope overlapping the integrin-binding motif in V2. The structure revealed that V1V2 assumes a five-stranded beta barrel structure with the region of the integrin-binding site (amino acids [aa] 179 to 181) included in a “kink” followed by an extra beta strand. The complete barrel structure naturally presents the glycans on its outer surface and packs into its core conserved hydrophobic residues, including the Ile at position 181 which was highly correlated with vaccine efficacy in RV144. The epitope of monoclonal antibody 830A is discontinuous and composed of three segments: (i) Thr175, Tyr177, Leu179, and Asp180at the kink overlapping the integrin-binding site; (ii) Arg153and Val154in V1; and (iii) Ile194at the C terminus of V2. Here, this report thus provides the atomic details of the immunogenic “V2i epitope.”},
doi = {10.1128/JVI.00754-15},
journal = {Journal of Virology},
number = 15,
volume = 89,
place = {United States},
year = {Wed Jul 08 00:00:00 EDT 2015},
month = {Wed Jul 08 00:00:00 EDT 2015}
}
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