Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

Science. 2007 Sep 28;317(5846):1930-4. doi: 10.1126/science.1145373.

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

Associated data

  • PDB/2QAD
  • PDB/2RLL