title: Understanding the molecular manipulation of DCAF1 by the lentiviral accessory proteins Vpr and Vpx.
abstract: Vpr and Vpx are primate lentivirus proteins that manipulate the cellular CRL4 ubiquitin ligase complex. While Vpr is common to all primate lentiviruses, Vpx is only encoded by HIV-2 and a limited range of SIVs. Although Vpr and Vpx share a high degree of homology they are known to induce markedly different effects in host cell biology through the recruitment of different substrates to CRL4. Here we explore the interaction of HIV-1 Vpr and SIVmac Vpx with the CRL4 substrate receptor DCAF1. Through mutational analysis of DCAF1 we demonstrate that although Vpr and Vpx share a highly similar DCAF1-binding motif, they interact with a different set of residues in DCAF1. In addition, we show that Vpx recruits SAMHD1 through a protein-protein interface that includes interactions of SAMHD1 with both Vpx and DCAF1, as was first suggested in crystallography data by (Schwefel, D., Groom, H.C.T., Boucherit, V.C., Christodoulou, E., Walker, P.A., Stoye, J.P., Bishop, K.N., Taylor, I.A., 2014. Structural basis of lentiviral subversion of a cellular protein degradation pathway., Nature, 505, 234-238).
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Cassiday
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Ana Beatriz
authors.initials: AB
authors.lastname: DePaula-Silva
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chumley
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ward
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Barker
authors.affiliation: Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East #2100, Salt Lake City, UT 84112, USA.
authors.forename: Vicente
authors.initials: V
authors.lastname: Planelles
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C513059:VPX protein, Simian immunodeficiency virus; D054334:Viral Regulatory and Accessory Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases; C530533:DCAF1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: DCAF1; DDB1; Degradation; HIV; Interaction; SAMHD1; SIV; Vpr; VprBP; Vpx