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

Authors

• Chih-chin Huang, National Institutes of Health
• Son N. Lam, National Institute of Diabetes and Digestive and Kidney Diseases
• Priyamvada Acharya, National Institutes of Health
• Min Tang, National Institutes of Health
• Shi-Hua Xiang, Harvard Medical SchoolFollow
• Syed Shahzad-ul Hussan, National Institute of Diabetes and Digestive and Kidney Diseases
• Robyn L. Stanfield, Scripps Research Institute
• James Robinson, Tulane University Medical Center
• Ian A. Wilson, Scripps Research InstituteFollow
• Richard Wyatt, National Institutes of Health
• Carole A. Bewley, National Institute of Diabetes and Digestive and Kidney DiseasesFollow
• Peter D. Kwong, National Institutes of HealthFollow

Document Type

Article

Date of this Version

2007

Comments

Published by Huang, Lam, Acharya, Tang, Xiang, Hussan, Stanfield, Robinson, Sodroski, Wilson, Wyatt, Bewley & Kwong in Science (September 28, 2007) 317, 1930-1935

Abstract

The CCR5 co-receptor binds to the HIV-l gp120 envelope glycoprotein and facilitates HIV-l 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 (α-helix) and 412d (extendedloop) 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-l 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.