title: Structural insights for HIV-1 therapeutic strategies targeting Vif.
abstract: HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is required for HIV-1 infection due largely to its role in recruiting antiretroviral factors of the APOBEC3 (apolipoprotein B editing catalytic subunit-like 3) family to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal degradation. The crystal structure of the (near) full-length Vif protein in complex with Elongin (Elo)B/C, core-binding factor (CBF)β and Cullin (Cul)5 revealed that Vif has a novel structural fold. In our opinion the structural data revealed not only the protein-protein interaction sites that determine Vif stability and interaction with cellular proteins, but also motifs driving Vif homodimerization, which are essential in Vif functionality and HIV-1 infection. Vif-mediated protein-protein interactions are excellent targets for a new class of antiretroviral therapeutics to combat AIDS.
authors.affiliation: OyaGen, Inc, 77 Ridgeland Road, Rochester, NY 14623, USA.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Salter
authors.affiliation: Cogent Professionals, 101 West Ohio Street, Suite 2000, Indianapolis, IN 46204, USA.
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Morales
authors.affiliation: OyaGen, Inc, 77 Ridgeland Road, Rochester, NY 14623, USA; University of Rochester, School of Medicine and Dentistry, Department of Biochemistry and Biophysics, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: hsmith@oyageninc.com.
authors.forename: Harold C
authors.initials: HC
authors.lastname: Smith
mesh_terms: D000071479:APOBEC-1 Deaminase; D000998:Antiviral Agents / Q000627:therapeutic use; D003564:Cytidine Deaminase / Q000378:metabolism; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D054320:vif Gene Products, Human Immunodeficiency Virus; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase
keywords: APOBEC; Elongin B/C; core-binding factor β; cullin 5; viral infectivity factor