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Science 28 September 2007:
Vol. 317. no. 5846, pp. 1930 - 1934
DOI: 10.1126/science.1145373
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Reports

Structures of the CCR5 N Terminus and of a Tyrosine-Sulfated Antibody with HIV-1 gp120 and CD4

Chih-chin Huang,1* Son N. Lam,2* Priyamvada Acharya,1 Min Tang,1 Shi-Hua Xiang,3 Syed Shahzad-ul Hussan,2 Robyn L. Stanfield,4 James Robinson,5 Joseph Sodroski,3 Ian A. Wilson,4 Richard Wyatt,1 Carole A. Bewley,2{dagger} Peter D. Kwong1{dagger}

The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 ({alpha}-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.

1 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
2 Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
3 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
4 Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
5 Department of Pediatrics, Tulane University Medical Center, New Orleans, LA 70112, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: caroleb{at}mail.nih.gov (C.A.B.); pdkwong{at}nih.gov (P.D.K.)

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