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 target cells. Acidic residues and sulfotyrosines in the amino-terminal domain (Nt) of CCR5 are crucial for viral fusion and entry. We tested the binding of a panel of CCR5 Nt peptides to different soluble gp120/CD4 complexes and anti-CCR5 mAbs. The tyrosine residues in the peptides were sulfated, phosphorylated, or unmodified. None of the gp120/CD4 complexes associated with peptides containing unmodified or phosphorylated tyrosines. The gp120/CD4 complexes containing envelope glycoproteins from isolates that use CCR5 as a coreceptor associated with Nt peptides containing sulfotyrosines but not with peptides containing sulfotyrosines in scrambled Nt sequences. Finally, only 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 domain determines the specificity of the interaction between CCR5 and gp120s from isolates that use this coreceptor.
Cormier
E G
EG
Albert Einstein College of Medicine, Microbiology and Immunology Department, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Persuh
M
M
Thompson
D A
DA
Lin
S W
SW
Sakmar
T P
TP
Olson
W C
WC
Dragic
T
T
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D000939:Epitopes / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000378:metabolism; D006801:Humans; D009052:Leukemia Virus, Murine / Q000378:metabolism; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000502:physiology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D046911:Macromolecular Substances; D010446:Peptide Fragments; D019713:Receptors, CCR5; C005662:tyrosine O-sulfate; D014443:Tyrosine