title: Exposed hydrophobic residues in human immunodeficiency virus type 1 Vpr helix-1 are important for cell cycle arrest and cell death.
abstract: The human immunodeficiency virus type 1 (HIV-1) accessory protein viral protein R (Vpr) is a major determinant for virus-induced G2/M cell cycle arrest and cytopathicity. Vpr is thought to perform these functions through the interaction with partner proteins. The NMR structure of Vpr revealed solvent exposed hydrophobic amino acids along helices 1 and 3 of Vpr, which could be putative protein binding domains. We previously showed that the hydrophobic patch along helix-3 was important for G2/M blockade and cytopathicity. Mutations of the exposed hydrophobic residues along helix-1 were found to reduce Vpr-induced cell cycle arrest and cell death as well. The levels of toxicity during virion delivery of Vpr correlated with G2/M arrest. Thus, the exposed hydrophobic amino acids in the amino-terminal helix-1 are important for the cell cycle arrest and cytopathicity functions of Vpr.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Barnitz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chaigne-Delalande
authors.forename: Diane L
authors.initials: DL
authors.lastname: Bolton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D017209:Apoptosis; D002455:Cell Division / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D016195:G2 Phase / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015497:HIV-1; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015151:Immunoblotting; D009154:Mutation / Q000235:genetics; D017433:Protein Structure, Secondary; D014771:Virion / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D054325:vpr Gene Products, Human Immunodeficiency Virus