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

被引：342

作者：

Huang, Chih-chin

Lam, Son N.

Acharya, Priyamvada

Tang, Min

Xiang, Shi-Hua

Hussan, Syed Shahzad-ul

Stanfield, Robyn L.

Robinson, James

Sodroski, Joseph

Wilson, Ian A.

Wyatt, Richard

Bewley, Carole A. ^{[1
]}

Kwong, Peter D.

机构：

[1] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[2] NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA

[4] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[6] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA

来源：

SCIENCE | 2007年 / 317卷 / 5846期

关键词：

D O I：

10.1126/science.1145373

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1930 / 1934

页数：5

共 29 条

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