title: The dileucine-based sorting motif in HIV-1 Nef is not required for down-regulation of class I MHC.
abstract: A dileucine-based protein sorting motif has recently been identified within the C-terminal, solvent-exposed loop of HIV-1 Nef and has been shown to be required for Nef-mediated down-regulation of CD4 and for optimal viral infectivity. Here, we report that mutation of the dileucine motif has no effect on Nef-mediated down-regulation of class I MHC heavy chain. Instead, deletion of an acidic domain just N-terminal of the polyproline helix of the SH3-binding domain significantly impairs this function. These data indicate that down-regulation of class I MHC and CD4 are mechanistically distinct processes. The data also suggest that protein interactions mediated by the acidic domain, rather than by the dileucine motif, may contribute to this function of Nef.
authors.affiliation: Department of Medicine, University of California, San Diego, CA, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Riggs
authors.forename: H M
authors.initials: HM
authors.lastname: Craig
authors.forename: M W
authors.initials: MW
authors.lastname: Pandori
authors.forename: J C
authors.initials: JC
authors.lastname: Guatelli
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000096:biosynthesis*; D006801:Humans; D007930:Leucine / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015789:HLA-A2 Antigen; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D007930:Leucine