Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, N.I.H., Intramural
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
-
Amino Acid Sequence
-
CD4 Antigens / chemistry*
-
CD4 Antigens / immunology
-
Crystallography, X-Ray
-
HIV Antibodies / chemistry*
-
HIV Antibodies / immunology
-
HIV Envelope Protein gp120 / chemistry*
-
HIV Envelope Protein gp120 / immunology
-
HIV Envelope Protein gp120 / metabolism
-
HIV-1 / metabolism
-
Humans
-
Models, Molecular
-
Molecular Mimicry
-
Molecular Sequence Data
-
Nuclear Magnetic Resonance, Biomolecular
-
Peptide Fragments / chemistry
-
Peptide Fragments / metabolism
-
Receptors, CCR5 / chemistry*
-
Receptors, CCR5 / metabolism
-
Sulfates / metabolism
-
Tyrosine / metabolism
-
Virus Internalization
Substances
-
CD4 Antigens
-
HIV Antibodies
-
HIV Envelope Protein gp120
-
HIV envelope protein gp120 (305-321)
-
Peptide Fragments
-
Receptors, CCR5
-
Sulfates
-
Tyrosine