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Science 11 November 2005:
Vol. 310. no. 5750, pp. 1025 - 1028
DOI: 10.1126/science.1118398
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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

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