title: Binding of soluble recombinant HIV envelope glycoprotein, rgp120, induces conformational changes in the cellular membrane-anchored CD4 molecule.
abstract: During HIV entry or resulting cell to cell fusion, the envelope glycoprotein gp120 binds first to the CD4 membrane distal domain and second to a chemokine receptor as coreceptor. Taking into consideration the relative length of these two molecules' extracellular parts, structural modulations of CD4 would be required to make the second interaction possible. In this work, we assessed the effect of gp120 binding on the conformation of CD4 expressed on cell surface. We demonstrated that following gp120 binding the avidity of some, but not all, monoclonal antibodies specific to epitopes, outside of the gp120-binding site, in D1, D3 and D4 domains of CD4 was decreased dramatically. This finding demonstrates that the gp120-CD4 interaction induces local and specific conformational changes of CD4 and constitutes functional evidence for hinge regions that could confer to this molecule the flexibility required for its various functions.
authors.affiliation: Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, 110 Avenue des Pins Ouest, Montreal, Quebec, H2W 1R7, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Yachou
authors.forename: R P
authors.initials: RP
authors.lastname: Sékaly
mesh_terms: D000911:Antibodies, Monoclonal; D000915:Antibody Affinity; D015704:CD4 Antigens / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D000939:Epitopes / Q000737:chemistry / Q000378:metabolism; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins