Specific interaction of CCR5 amino-terminal domain peptides containing sulfotyrosines with HIV-1 envelope glycoprotein gp120

The HIV-1 envelope glycoprotein gp120 interacts consecutively with CD4 and the CCR5 coreceptor to mediate the entry of certain HIV-1 strains into targ et cells. Acidic residues and sulfotyrosines in the amino-terminal domain ( Nt) of CCR5 are crucial for viral fusion and entry. We tested the binding o f a panel of CCR5 Nt peptides to different soluble gp120/CD4 complexes and anti-CCR5 mAbs, The tyrosine residues in the peptides were sulfated, phosph orylated, or unmodified. None of the gp120/CD4 complexes associated with pe ptides containing unmodified or phosphorylated tyrosines, The gp120/CD4 com plexes containing envelope glycoproteins from isolates that use CCR5 as a c oreceptor associated with Nt peptides containing sulfotyrosines but not wit h peptides containing sulfotyrosines in scrambled Nt sequences. Finally, on ly peptides containing sulfotyrosines inhibited the entry of an R5 isolate. Our data show that proper posttranslational modification of the CCR5 Nt is required for gp120 binding and viral entry. More importantly, the Nt domai n determines the specificity of the interaction between CCR5 and gp120s fro m isolates that use this coreceptor.