Structure-function relationship of Vpr: biological implications.
Vpr, incorporated into the HIV-1 virion, shows multiple activities including nuclear transport of the preintegration complex to the nucleus, activation of the transcription, cell cycle arrest at the G2/M transition and induction of apoptosis. Vpr controls many host cell functions through a variety of biological activities and by interaction with cellular biochemical pathways. Nuclear import of Vpr may be due to its interaction with nuclear transport factors and components of the nuclear pore complex. Cell cycle arrest has been correlated with the binding to DCAF1, a cullin 4A-associated factor and apoptosis may be facilitated by interaction with mitochondrial proteins, in a caspase-dependent mechanism. The structure of Vpr(1-96) and various fragments have been determined by NMR in diverse solvents. The different functions of Vpr can be classified according to their relationship with the different structural domains of the protein and appear to correlate with the partners interacting with these domains. Thus, virion packaging seems to be mediated by the first alpha-helix (17-33), activation of the transcription, regulation of apoptosis and subcellular transport appear to be dependent on the second alpha-helix (38-50) and cell cycle arrest seems to be induced by the carboxyl terminal alpha-helix (55-77). Mutational analysis performed by several groups have provided a strong basis to understand the structure-function relationship of Vpr. The aim of this review is to run through these mutations using the available information on sequences and discuss their effect on the functions of Vpr from the point of view of its structure.
Morellet
Nelly
N
Inserm, U640, Paris, France. nelly.morellet@univ-paris5.fr
Roques
Bernard P
BP
Bouaziz
Serge
S
D004252:DNA Mutational Analysis; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D037521:Virulence Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1