title: Herpes simplex virus inhibitor ICP47 destabilizes the transporter associated with antigen processing (TAP) heterodimer.
abstract: Chemical cross-linking of the transporter associated with antigen processing (TAP) heterodimer was used to determine whether the herpes simplex virus inhibitor of TAP, ICP47, induces a conformational change in TAP. Cross-linking of TAP in cellular membranes produced a major species of approximately 220 kDa which was comprised solely of TAP.1 and TAP.2 and most likely represents the TAP heterodimer. Interestingly, prior treatment of TAP-containing membranes with TAP peptide substrates stimulated the formation of the cross-linked TAP heterodimer, whereas pretreatment of membranes with ICP47 completely blocked the formation of the cross-linked heterodimer. These data suggest that suitable substrates for TAP stabilize the TAP heterodimer, whereas ICP47 destabilizes the heterodimer. The results indicate that subtle conformational changes occur in the TAP heterodimer upon the binding of peptides and the inhibitor ICP47 and that ICP47 has a deleterious effect on TAP heterodimer structure, in addition to its role as a potent blocker of substrate binding to TAP.
authors.affiliation: Immunology Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida College of Medicine, Tampa, Florida 33612, USA.
authors.forename: V G
authors.initials: VG
authors.lastname: Lacaille
authors.forename: M J
authors.initials: MJ
authors.lastname: Androlewicz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors*; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D019281:Dimerization; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007457:Iodine Radioisotopes; D018411:Spodoptera; D014764:Viral Proteins
chemical_list: D018528:ATP-Binding Cassette Transporters; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D007457:Iodine Radioisotopes; D014764:Viral Proteins