Interactions of the C-terminus of viral protein R with nucleic acids are modulated by its N-terminus.
The basic viral protein R (Vpr) performs several functions during the human immunodeficiency virus HIV-1 retroviral cycle, including G2 mitosis arrest and nuclear import of the preintegration complex allowing lentivirus to replicate in nondividing cells. Accordingly, this protein was found in the nucleus of infected cells. In the virus, Vpr is incorporated through interaction with both nucleocapsid protein 7 (NCp7) and p6, two small proteins encoded by the C-terminal part of the Gag precursor. NCp7 is also involved in genomic RNA encapsidation during the budding process suggesting a possible interaction of Vpr with nucleic acids, either directly or via the NCp7 intermediate. Gel shift experiments were carried out with RNA and DNA using synthetic Vpr and peptide derivatives. The results show that Vpr binds to nucleic-acid inducing aggregates. This process, which requires the C-terminal basic domain of the protein (in particular the helical 70-80 domain), is regulated by the N-terminal region of Vpr. Moreover, NCp7 was shown to enhance RNA recognition by Vpr, a feature that could be required for Vpr encapsidation and during nuclear import of the preintegration complex.
de Rocquigny
H
H
Département de Pharmacochimie Moléculaire et Structurale, INSERM U266, CNRS UMR 8600, Faculté de Pharmacie 4, Paris, France.
Caneparo
A
A
Delaunay
T
T
Bischerour
J
J
Mouscadet
J F
JF
Roques
B P
BP
D000595:Amino Acid Sequence; D001665:Binding Sites; D002213:Capsid / Q000378:metabolism; D036022:Capsid Proteins; D004279:DNA, Viral / Q000378:metabolism*; D015683:Gene Products, gag / Q000378:metabolism; D016336:Gene Products, vpr / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus
D036022:Capsid Proteins; D004279:DNA, Viral; D015683:Gene Products, gag; D016336:Gene Products, vpr; C071884:NCP7 protein, Human immunodeficiency virus 1; D010446:Peptide Fragments; D012367:RNA, Viral; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; D054325:vpr Gene Products, Human Immunodeficiency Virus