Identification of Amino Acid Residues in CD81 Critical for Interaction with Hepatitis C Virus Envelope Glycoprotein E2
- 15 April 2000
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 74 (8), 3642-3649
- https://doi.org/10.1128/jvi.74.8.3642-3649.2000
Abstract
Human CD81 has been previously identified as the putative receptor for the hepatitis C virus envelope glycoprotein E2. The large extracellular loop (LEL) of human CD81 differs in four amino acid residues from that of the African green monkey (AGM), which does not bind E2. We mutated each of the four positions in human CD81 to the corresponding AGM residues and expressed them as soluble fusion LEL proteins in bacteria or as complete membrane proteins in mammalian cells. We found human amino acid 186 to be critical for the interaction with the viral envelope glycoprotein. This residue was also important for binding of certain anti-CD81 monoclonal antibodies. Mutating residues 188 and 196 did not affect E2 or antibody binding. Interestingly, mutation of residue 163 increased both E2 and antibody binding, suggesting that this amino acid contributes to the tertiary structure of CD81 and its ligand-binding ability. These observations have implications for the design of soluble high-affinity molecules that could target the CD81-E2 interaction site(s).This publication has 17 references indexed in Scilit:
- Role of Transmembrane 4 Superfamily (Tm4sf) Proteins Cd9 and Cd81 in Muscle Cell Fusion and Myotube MaintenanceThe Journal of cell biology, 1999
- Characterization of Hepatitis C Virus E2 Glycoprotein Interaction with a Putative Cellular Receptor, CD81Journal of Virology, 1999
- TCR Vaccines Against T Cell Lymphoma: QS-21 and IL-12 Adjuvants Induce a Protective CD8+ T Cell ResponseThe Journal of Immunology, 1999
- CD81 (TAPA-1): A MOLECULE INVOLVED IN SIGNAL TRANSDUCTION AND CELL ADHESION IN THE IMMUNE SYSTEMAnnual Review of Immunology, 1998
- CD81 expressed on human thymocytes mediates integrin activation and interleukin 2-dependent proliferation.The Journal of Experimental Medicine, 1996
- The CD19/CR2/TAPA-1 Complex of B Lymphocytes: Linking Natural to Acquired ImmunityAnnual Review of Immunology, 1995
- Extrahepatic Immunologic Manifestations in Chronic Hepatitis C and Hepatitis C Virus SerotypesAnnals of Internal Medicine, 1995
- TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins.Molecular and Cellular Biology, 1990
- Site-directed mutagenesis by overlap extension using the polymerase chain reactionGene, 1989
- The measurement of relative antibody affinity by ELISA using thiocyanate elutionJournal of Immunological Methods, 1988