Identification of the hepatitis C virus E2 glycoprotein binding site on the large extracellular loop of CD81.
The binding of hepatitis C virus glycoprotein E2 to the large extracellular loop (LEL) of CD81 has been shown to modulate human T-cell and NK cell activity in vitro. Using random mutagenesis of a chimera of maltose-binding protein and LEL residues 113 to 201, we have determined that the E2-binding site on CD81 comprises residues Ile(182), Phe(186), Asn(184), and Leu(162). These findings reveal an E2-binding surface of approximately 806 A(2) and potential target sites for the development of small-molecule inhibitors of E2 binding.
D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002461:Cell Line, Transformed; D016174:Hepacivirus / Q000378:metabolism*; D018936:Hepatitis C Antigens / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000378:metabolism*
D015703:Antigens, CD; C554798:CD81 protein, human; D018936:Hepatitis C Antigens; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus