title: Envelope glycoprotein cytoplasmic domains from diverse lentiviruses interact with the prenylated Rab acceptor.
abstract: Lentivirus envelope glycoproteins have unusually long cytoplasmic domains compared to those of other retroviruses. To identify cellular binding partners of the simian immunodeficiency virus (SIV) envelope transmembrane protein (gp41) cytoplasmic domain (CD), we performed a yeast two-hybrid screen of a phytohemagglutinin-activated human T-cell cDNA library with the SIV gp41 CD. The majority of positive clones (50 of 54) encoded the prenylated Rab acceptor (PRA1). PRA1 is a 21-kDa protein associated with Golgi membranes that binds to prenylated Rab proteins in their GTP-bound state. While the cellular function of PRA1 is presently unknown, this protein appears to participate in intracellular vesicular trafficking, based on its cellular localization and ability to bind multiple members of the Rab protein family. Mammalian two-hybrid assays confirmed the interaction between the SIV gp41 CD and PRA1. Furthermore, gp41 sequences important for PRA1 binding were mapped to a central leucine-rich, amphipathic alpha-helix in the SIV gp41 cytoplasmic tail. Although the human immunodeficiency virus (HIV-1) gp41 CD failed to interact with PRA1 in the yeast two-hybrid system, its interaction with PRA1 was significantly better than that of the SIV gp41 CD in mammalian two-hybrid assays. Interestingly, PRA1 also interacted with the Env CDs of HIV-2, bovine immunodeficiency virus, equine infectious anemia virus, and feline immunodeficiency virus. Thus, PRA1 associates with envelope glycoproteins from widely divergent lentiviruses.
authors.affiliation: New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
authors.forename: Karl C
authors.initials: KC
authors.lastname: Tillman
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Desrosiers
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D019204:GTP-Binding Proteins; D006801:Humans; D016086:Lentivirus / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011485:Protein Binding; D012191:Retroviridae Proteins / Q000737:chemistry / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D012191:Retroviridae Proteins; C082614:SIV envelope protein gp41; D033921:Vesicular Transport Proteins; D014759:Viral Envelope Proteins; D019204:GTP-Binding Proteins; C108941:RABAC1 protein, human