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

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.