Abstract
Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is posttranslationally modified by O-linked glycosylation and by sulfation of its N-terminal tyrosines. Sulfated tyrosines contribute to the binding 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, another important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may contribute to the natural function of many 7TMS receptors and may be a modification common to primate immunodeficiency virus coreceptors.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
CD4 Antigens / metabolism
-
Carbohydrate Conformation
-
Cells, Cultured
-
Chemokine CCL4
-
Chlorates / pharmacology
-
Dogs
-
Glycosylation
-
HIV Envelope Protein gp120 / metabolism
-
HIV-1 / physiology*
-
HeLa Cells
-
Humans
-
Macrophage Inflammatory Proteins / metabolism
-
Molecular Sequence Data
-
Protein Processing, Post-Translational* / drug effects
-
Receptors, CCR5 / chemistry*
-
Receptors, CCR5 / physiology
-
Receptors, CXCR4 / chemistry
-
Receptors, CXCR4 / physiology
-
Recombinant Fusion Proteins / metabolism
-
Sequence Alignment
-
Sequence Homology, Amino Acid
-
Sulfotransferases / metabolism
-
Tumor Cells, Cultured
-
Tyrosine / analogs & derivatives*
-
Tyrosine / biosynthesis
-
Tyrosine / physiology
Substances
-
CD4 Antigens
-
Chemokine CCL4
-
Chlorates
-
HIV Envelope Protein gp120
-
Macrophage Inflammatory Proteins
-
Receptors, CCR5
-
Receptors, CXCR4
-
Recombinant Fusion Proteins
-
tyrosine O-sulfate
-
Tyrosine
-
Sulfotransferases