Vpr

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VPR
PDB 1fi0 EBI.jpg
solution structure of hiv-1 vpr (13-33) peptide in micells
Identifiers
Symbol VPR
Pfam PF00522
InterPro IPR000012
SCOP 1dsk
SUPERFAMILY 1dsk
TCDB 1.A.42

Vpr is a Human immunodeficieny viral gene and protein product.[1][2]

Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for virus replication in non-dividing cells such as macrophages. Vpr also induces G2 cell cycle arrest and apoptosis in proliferating cells, which can result in immune dysfunction.[3][4]

Vpr is also immunosuppressive due to its ability to sequester a proinflammatory transcriptional activator in the cytoplasm. HIV-2 contains both a Vpr protein and a related (by sequence homology) Vpx protein (Viral Protein X). Two functions of Vpr in HIV-1 are split between Vpr and Vpx in HIV-2, with the HIV-2 Vpr protein inducing cell cycle arrest and the Vpx protein required for nuclear import.

Vpr-Binding Protein[edit]

Vpr-binding protein (VprBP) is a 1,507-amino-acid human protein that contains conserved domains, including YXXY repeats, the Lis homology motif, and WD40 repeats.[5] VprBP acts as a substrate-recognition unit when associated with DNA damage-binding protein 1 (DDB1) as part of a CUL4–DDB1 E3 ubiquitin ligase complex.[5] When bound to Vpr, VprBP allows Vpr to modulate the catalytic activity of the CUL4–DDB1 complex, inducing G2 cell cycle arrest in infected cells.[5]

VprBP also regulates p53-induced transcription and apoptotic pathways. p53 is an important tumor suppressor which induces either cell cycle arrest or apoptosis in response to DNA damage.[5]

References[edit]

  1. ^ Vpr Gene Products, Human Immunodeficiency Virus at the US National Library of Medicine Medical Subject Headings (MeSH)
  2. ^ Genes, Vpr at the US National Library of Medicine Medical Subject Headings (MeSH)
  3. ^ Bukrinsky M, Adzhubei A (1999). "Viral protein R of HIV-1". Rev. Med. Virol. 9 (1): 39–49. doi:10.1002/(SICI)1099-1654(199901/03)9:1<39::AID-RMV235>3.0.CO;2-3. PMID 10371671. 
  4. ^ Muthumani K, Choo AY, Zong WX, et al. (February 2006). "The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1". Nat. Cell Biol. 8 (2): 170–9. doi:10.1038/ncb1352. PMC 3142937. PMID 16429131. 
  5. ^ a b c d Kim K, Heo K, Choi J, Jackson S, Kim H, Xiong Y et al. (2012). "Vpr-binding protein antagonizes p53-mediated transcription via direct interaction with H3 tail.". Mol Cell Biol 32 (4): 783–96. doi:10.1128/MCB.06037-11. PMC 3272969. PMID 22184063.