Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry

Chemokine receptors and related seven-transmembrane-segment (7TMS) receptor s serve as coreceptors for entry of human and simian immunodeficiency virus es (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diver se coreceptors contains an N-terminal region that is acidic and tyrosine ri ch. Here, we show that the chemokine receptor CCR5, a principal HIV-1 corec eptor, is posttranslationally modified by O-linked glycosylation and by sul fation of its N-terminal tyrosines. Sulfated tyrosines contribute to the bi nding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells expressing CCR5 and CD4. CXCR4, ano ther important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may c ontribute to the natural function of many 7TMS receptors and may be a modif ication common to primate immunodeficiency virus coreceptors.