Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

Chih Chin Huang, Son N. Lam, Priyamvada Acharya, Min Tang, Shi Hua Xiang, Syed Shahzad-Ul-Hussan, Robyn L. Stanfield, James Robinson, Joseph Sodroski, Ian A. Wilson, Richard Wyatt, Carole A. Bewley, Peter D. Kwong

Research output: Contribution to journalArticlepeer-review

327 Scopus citations

Abstract

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 (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-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.

Original languageEnglish (US)
Pages (from-to)1930-1934
Number of pages5
JournalScience
Volume317
Issue number5846
DOIs
StatePublished - Sep 28 2007
Externally publishedYes

ASJC Scopus subject areas

  • General

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