Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 11 November 2005:
Vol. 310. no. 5750, pp. 1025 - 1028
DOI: 10.1126/science.1118398
Prev | Table of Contents | Next

Reports

Structure of a V3-Containing HIV-1 gp120 Core

Chih-chin Huang,1 Min Tang,1 Mei-Yun Zhang,2 Shahzad Majeed,1 Elizabeth Montabana,1 Robyn L. Stanfield,4 Dimiter S. Dimitrov,3 Bette Korber,5 Joseph Sodroski,6 Ian A. Wilson,4 Richard Wyatt,1* Peter D. Kwong1*

The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization.

1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
2 Basic Research Program, SAIC-Frederick, Center for Cancer Research Nanobiology Program, National Cancer Institute, Frederick, MD 21702, USA.
3 Protein Interaction Group, Center for Cancer Research Nanobiology Program, National Cancer Institute, Frederick, MD 21702, USA.
4 Department of Molecular Biology and Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
5 Theoretical Biology (T10), Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
6 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

* To whom correspondence should be addressed. E-mail: richw{at}mail.nih.gov;pdkwong@nih.gov

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Tissue-Specific Sequence Alterations in the Human Immunodeficiency Virus Type 1 Envelope Favoring CCR5 Usage Contribute to Persistence of Dual-Tropic Virus in the Brain.
L. Gray, M. Roche, M. J. Churchill, J. Sterjovski, A. Ellett, P. Poumbourios, S. Sheffief, B. Wang, N. Saksena, D. F. J. Purcell, et al. (2009)
J. Virol. 83, 5430-5441
   Abstract »    Full Text »    PDF »
Enhanced Exposure of the CD4-Binding Site to Neutralizing Antibodies by Structural Design of a Membrane-Anchored Human Immunodeficiency Virus Type 1 gp120 Domain.
L. Wu, T. Zhou, Z.-y. Yang, K. Svehla, S. O'Dell, M. K. Louder, L. Xu, J. R. Mascola, D. R. Burton, J. A. Hoxie, et al. (2009)
J. Virol. 83, 5077-5086
   Abstract »    Full Text »    PDF »
Selection of a Simian-Human Immunodeficiency Virus Strain Resistant to a Vaginal Microbicide in Macaques.
D. M. Dudley, J. L. Wentzel, M. S. Lalonde, R. S. Veazey, and E. J. Arts (2009)
J. Virol. 83, 5067-5076
   Abstract »    Full Text »    PDF »
Amino Acid Covariation in a Functionally Important Human Immunodeficiency Virus Type 1 Protein Region Is Associated With Population Subdivision.
J. da Silva (2009)
Genetics 182, 265-275
   Abstract »    Full Text »    PDF »
Characterization of a Human Immunodeficiency Virus Type 1 V3 Deletion Mutation That Confers Resistance to CCR5 Inhibitors and the Ability To Use Aplaviroc-Bound Receptor.
K. M. Nolan, G. Q. Del Prete, A. P. O. Jordan, B. Haggarty, J. Romano, G. J. Leslie, and J. A. Hoxie (2009)
J. Virol. 83, 3798-3809
   Abstract »    Full Text »    PDF »
Determinants Flanking the CD4 Binding Loop Modulate Macrophage Tropism of Human Immunodeficiency Virus Type 1 R5 Envelopes.
M. J. Duenas-Decamp, P. J. Peters, D. Burton, and P. R. Clapham (2009)
J. Virol. 83, 2575-2583
   Abstract »    Full Text »    PDF »
The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions.
R. Pantophlet, M. Wang, R. O. Aguilar-Sino, and D. R. Burton (2009)
J. Virol. 83, 1649-1659
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 2 (HIV-2)/HIV-1 Envelope Chimeras Detect High Titers of Broadly Reactive HIV-1 V3-Specific Antibodies in Human Plasma.
K. L. Davis, F. Bibollet-Ruche, H. Li, J. M. Decker, O. Kutsch, L. Morris, A. Salomon, A. Pinter, J. A. Hoxie, B. H. Hahn, et al. (2009)
J. Virol. 83, 1240-1259
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Type 1 Env Trimer Immunization of Macaques and Impact of Priming with Viral Vector or Stabilized Core Protein.
A. Morner, I. Douagi, M. N. E. Forsell, C. Sundling, P. Dosenovic, S. O'Dell, B. Dey, P. D. Kwong, G. Voss, R. Thorstensson, et al. (2009)
J. Virol. 83, 540-551
   Abstract »    Full Text »    PDF »
Focus on antivirally active sulfated polysaccharides: From structure-activity analysis to clinical evaluation.
T. Ghosh, K. Chattopadhyay, M. Marschall, P. Karmakar, P. Mandal, and B. Ray (2009)
Glycobiology 19, 2-15
   Abstract »    Full Text »    PDF »
Role of the HIV gp120 Conserved Domain 1 in Processing and Viral Entry.
J. Wang, J. Sen, L. Rong, and M. Caffrey (2008)
J. Biol. Chem. 283, 32644-32649
   Abstract »    Full Text »    PDF »
Identification of Monomorphic and Divergent Haplotypes in the 2006-2007 Norovirus GII/4 Epidemic Population by Genomewide Tracing of Evolutionary History.
K. Motomura, T. Oka, M. Yokoyama, H. Nakamura, H. Mori, H. Ode, G. S. Hansman, K. Katayama, T. Kanda, T. Tanaka, et al. (2008)
J. Virol. 82, 11247-11262
   Abstract »    Full Text »    PDF »
Importance of the V1/V2 Loop Region of Simian-Human Immunodeficiency Virus Envelope Glycoprotein gp120 in Determining the Strain Specificity of the Neutralizing Antibody Response.
M. E. Laird, T. Igarashi, M. A. Martin, and R. C. Desrosiers (2008)
J. Virol. 82, 11054-11065
   Abstract »    Full Text »    PDF »
Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers.
W. Chen, Z. Zhu, Y. Feng, and D. S. Dimitrov (2008)
PNAS 105, 17121-17126
   Abstract »    Full Text »    PDF »
Mapping of the CXCR4 Binding Site within Variable Region 3 of the Feline Immunodeficiency Virus Surface Glycoprotein.
M. Sundstrom, R. L. White, A. de Parseval, K. J. Sastry, G. Morris, C. K. Grant, and J. H. Elder (2008)
J. Virol. 82, 9134-9142
   Abstract »    Full Text »    PDF »
Improved Induction of Antibodies against Key Neutralizing Epitopes by Human Immunodeficiency Virus Type 1 gp120 DNA Prime-Protein Boost Vaccination Compared to gp120 Protein-Only Vaccination.
M. Vaine, S. Wang, E. T. Crooks, P. Jiang, D. C. Montefiori, J. Binley, and S. Lu (2008)
J. Virol. 82, 7369-7378
   Abstract »    Full Text »    PDF »
R5X4 Viruses Are Evolutionary, Functional, and Antigenic Intermediates in the Pathway of a Simian-Human Immunodeficiency Virus Coreceptor Switch.
S. Tasca, S.-H. Ho, and C. Cheng-Mayer (2008)
J. Virol. 82, 7089-7099
   Abstract »    Full Text »    PDF »
The HIV-1 Envelope Glycoprotein gp120 Features Four Heparan Sulfate Binding Domains, Including the Co-receptor Binding Site.
E. Crublet, J.-P. Andrieu, R. R. Vives, and H. Lortat-Jacob (2008)
J. Biol. Chem. 283, 15193-15200
   Abstract »    Full Text »    PDF »
Mutational analysis of a principal neutralization domain of visna/maedi virus envelope glycoprotein.
B. S. Haflidadottir, S. Matthiasdottir, G. Agnarsdottir, S. Torsteinsdottir, G. Petursson, O. S. Andresson, and V. Andresdottir (2008)
J. Gen. Virol. 89, 716-721
   Abstract »    Full Text »    PDF »
Conformational Rearrangement within the Soluble Domains of the CD4 Receptor Is Ligand-specific.
Ashish, I. J. Juncadella, R. Garg, C. D. Boone, J. Anguita, and J. K. Krueger (2008)
J. Biol. Chem. 283, 2761-2772
   Abstract »    Full Text »    PDF »
Effects of Partial Deletions within the Human Immunodeficiency Virus Type 1 V3 Loop on Coreceptor Tropism and Sensitivity to Entry Inhibitors.
K. M. Nolan, A. P. O. Jordan, and J. A. Hoxie (2008)
J. Virol. 82, 664-673
   Abstract »    Full Text »    PDF »
Subtype-Specific Conformational Differences within the V3 Region of Subtype B and Subtype C Human Immunodeficiency Virus Type 1 Env Proteins.
M. B. Patel, N. G. Hoffman, and R. Swanstrom (2008)
J. Virol. 82, 903-916
   Abstract »    Full Text »    PDF »
Betulinic Acid Derivatives That Target gp120 and Inhibit Multiple Genetic Subtypes of Human Immunodeficiency Virus Type 1.
W. Lai, L. Huang, P. Ho, Z. Li, D. Montefiori, and C.-H. Chen (2008)
Antimicrob. Agents Chemother. 52, 128-136
   Abstract »    Full Text »    PDF »
A Study of the Coevolutionary Patterns Operating within the env Gene of the HIV-1 Group M Subtypes.
S. A. A. Travers, D. C. Tully, G. P. McCormack, and M. A. Fares (2007)
Mol. Biol. Evol. 24, 2787-2801
   Abstract »    Full Text »    PDF »
Inhibitory role of CXCR4 glycan in CD4-independent X4-tropic human immunodeficiency virus type 1 infection and its abrogation in CD4-dependent infection.
Y. Kubo, M. Yokoyama, H. Yoshii, C. Mitani, C. Tominaga, Y. Tanaka, H. Sato, and N. Yamamoto (2007)
J. Gen. Virol. 88, 3139-3144
   Abstract »    Full Text »    PDF »
Towards Covalent Vaccination: IMPROVED POLYCLONAL HIV NEUTRALIZING ANTIBODY RESPONSE INDUCED BY AN ELECTROPHILIC gp120 V3 PEPTIDE ANALOG.
Y. Nishiyama, Y. Mitsuda, H. Taguchi, S. Planque, M. Salas, C. V. Hanson, and S. Paul (2007)
J. Biol. Chem. 282, 31250-31256
   Abstract »    Full Text »    PDF »
N-Linked Glycan Modifications in gp120 of Human Immunodeficiency Virus Type 1 Subtype C Render Partial Sensitivity to 2G12 Antibody Neutralization.
E. S. Gray, P. L. Moore, R. A. Pantophlet, and L. Morris (2007)
J. Virol. 81, 10769-10776
   Abstract »    Full Text »    PDF »
Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4.
C.-c. Huang, S. N. Lam, P. Acharya, M. Tang, S.-H. Xiang, S. S.-u. Hussan, R. L. Stanfield, J. Robinson, J. Sodroski, I. A. Wilson, et al. (2007)
Science 317, 1930-1934
   Abstract »    Full Text »    PDF »
Replication-Competent Variants of Human Immunodeficiency Virus Type 2 Lacking the V3 Loop Exhibit Resistance to Chemokine Receptor Antagonists.
G. Lin, A. Bertolotti-Ciarlet, B. Haggarty, J. Romano, K. M. Nolan, G. J. Leslie, A. P.-O. Jordan, C.-c. Huang, P. D. Kwong, R. W. Doms, et al. (2007)
J. Virol. 81, 9956-9966
   Abstract »    Full Text »    PDF »
Expression and Characterization of a Minimal Hepatitis C Virus Glycoprotein E2 Core Domain That Retains CD81 Binding.
K. McCaffrey, I. Boo, P. Poumbourios, and H. E. Drummer (2007)
J. Virol. 81, 9584-9590
   Abstract »    Full Text »    PDF »
Natural Variation in the V3 Crown of Human Immunodeficiency Virus Type 1 Affects Replicative Fitness and Entry Inhibitor Sensitivity.
M. A. Lobritz, A. J. Marozsan, R. M. Troyer, and E. J. Arts (2007)
J. Virol. 81, 8258-8269
   Abstract »    Full Text »    PDF »
Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120.
P. W.-P. Hong, S. Nguyen, S. Young, S. V. Su, and B. Lee (2007)
J. Virol. 81, 8325-8336
   Abstract »    Full Text »    PDF »
Stability of a Receptor-Binding Active Human Immunodeficiency Virus Type 1 Recombinant gp140 Trimer Conferred by Intermonomer Disulfide Bonding of the V3 Loop: Differential Effects of Protein Disulfide Isomerase on CD4 and Coreceptor Binding.
J. Billington, T. P. Hickling, G. H. Munro, C. Halai, R. Chung, G. G. Dodson, and R. S. Daniels (2007)
J. Virol. 81, 4604-4614
   Abstract »    Full Text »    PDF »
Impact of V2 Mutations on Escape from a Potent Neutralizing Anti-V3 Monoclonal Antibody during In Vitro Selection of a Primary Human Immunodeficiency Virus Type 1 Isolate.
J. Shibata, K. Yoshimura, A. Honda, A. Koito, T. Murakami, and S. Matsushita (2007)
J. Virol. 81, 3757-3768
   Abstract »    Full Text »    PDF »
Antigenic and Immunogenic Study of Membrane-Proximal External Region-Grafted gp120 Antigens by a DNA Prime-Protein Boost Immunization Strategy.
M. Law, R. M. F. Cardoso, I. A. Wilson, and D. R. Burton (2007)
J. Virol. 81, 4272-4285
   Abstract »    Full Text »    PDF »
Broad-Spectrum Anti-Human Immunodeficiency Virus (HIV) Potential of a Peptide HIV Type 1 Entry Inhibitor.
S. Cocklin, H. Gopi, B. Querido, M. Nimmagadda, S. Kuriakose, C. Cicala, S. Ajith, S. Baxter, J. Arthos, J. Martin-Garcia, et al. (2007)
J. Virol. 81, 3645-3648
   Abstract »    Full Text »    PDF »
Time Frames for Neutralization during the Human Immunodeficiency Virus Type 1 Entry Phase, as Monitored in Synchronously Infected Cell Cultures.
H. Haim, I. Steiner, and A. Panet (2007)
J. Virol. 81, 3525-3534
   Abstract »    Full Text »    PDF »
Production and characterization of monoclonal antibodies sensitive to conformation in the 5HT2c serotonin receptor.
F. Mancia, S. Brenner-Morton, R. Siegel, Z. Assur, Y. Sun, I. Schieren, M. Mendelsohn, R. Axel, and W. A. Hendrickson (2007)
PNAS 104, 4303-4308
   Abstract »    Full Text »    PDF »
Physiological Levels of Virion-Associated Human Immunodeficiency Virus Type 1 Envelope Induce Coreceptor-Dependent Calcium Flux.
M. Melar, D. E. Ott, and T. J. Hope (2007)
J. Virol. 81, 1773-1785
   Abstract »    Full Text »    PDF »
HIV gp120-induced Interaction between CD4 and CCR5 Requires Cholesterol-rich Microenvironments Revealed by Live Cell Fluorescence Resonance Energy Transfer Imaging.
L. Yi, J. Fang, N. Isik, J. Chim, and T. Jin (2006)
J. Biol. Chem. 281, 35446-35453
   Abstract »    Full Text »    PDF »
Novel Envelope Determinants for CCR3 Use by Human Immunodeficiency Virus..
M. M. I. Aasa-Chapman, C. R. Seymour, I. Williams, and A. McKnight (2006)
J. Virol. 80, 10884-10889
   Abstract »    Full Text »    PDF »
The HIV Env variant N283 enhances macrophage tropism and is associated with brain infection and dementia.
R. L. Dunfee, E. R. Thomas, P. R. Gorry, J. Wang, J. Taylor, K. Kunstman, S. M. Wolinsky, and D. Gabuzda (2006)
PNAS 103, 15160-15165
   Abstract »    Full Text »    PDF »
Molecular switch for alternative conformations of the HIV-1 V3 region: Implications for phenotype conversion.
O. Rosen, M. Sharon, S. R. Quadt-Akabayov, and J. Anglister (2006)
PNAS 103, 13950-13955
   Abstract »    Full Text »    PDF »
Mutational Pathways, Resistance Profile, and Side Effects of Cyanovirin Relative to Human Immunodeficiency Virus Type 1 Strains with N-Glycan Deletions in Their gp120 Envelopes..
J. Balzarini, K. Van Laethem, W. J. Peumans, E. J. M. Van Damme, A. Bolmstedt, F. Gago, and D. Schols (2006)
J. Virol. 80, 8411-8421
   Abstract »    Full Text »    PDF »
Structure of Severe Acute Respiratory Syndrome Coronavirus Receptor-binding Domain Complexed with Neutralizing Antibody.
P. Prabakaran, J. Gan, Y. Feng, Z. Zhu, V. Choudhry, X. Xiao, X. Ji, and D. S. Dimitrov (2006)
J. Biol. Chem. 281, 15829-15836
   Abstract »    Full Text »    PDF »
Crystal Structures of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralizing Antibody 2219 in Complex with Three Different V3 Peptides Reveal a New Binding Mode for HIV-1 Cross-Reactivity..
R. L. Stanfield, M. K. Gorny, S. Zolla-Pazner, and I. A. Wilson (2006)
J. Virol. 80, 6093-6105
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)