Vpr protein

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== Function ==
== Function ==
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'''Vpr protein''' (Vpr) or '''viral protein R''' is a 96 amino acid protein which encoded by the human Immunodeficiency virus type 1 ([[HIV-1]]). Vpr has several roles in the progression of acquired immunodeficiency syndrome (AIDS) disease, including regulation the HIV-1 pre-integration complex ({{Wikipedia|Pre-integration_complex}}) nuclear import and virus replication in non-dividing macrophages<ref>PMID:12614620</ref>. Moreover, Vpr prevents mitosis of dividing infect cells by blockade at G2 phase, when the viral promoter is more active, and induced apoptosis of these cells in G1 and M phase. Both the activities of cell cycle arrest and induce apoptosis has proven to be independence by mutations that can cause only one of these affects<ref>PMID:28075409</ref>.
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'''Vpr protein''' (Vpr) or '''viral protein R''' is a 96 amino acid protein which encoded by the human Immunodeficiency virus type 1 ([[HIV-1]]). HIV-1 genome includes nine genes, six of them are accessory proteins, including ''vpr''. Vpr has several roles in the progression of acquired immunodeficiency syndrome ([https://en.wikipedia.org/wiki/AIDS AIDS]) disease, including regulation the HIV-1 pre-integration complex ([https://en.wikipedia.org/wiki/Pre-integration_complex PIC]) nuclear import and virus replication in non-dividing macrophages<ref name='Morellet2003'>PMID:12614620</ref>. Moreover, Vpr prevents mitosis of dividing infect cells by blockade at G2 phase, when the viral promoter is more active, and induced apoptosis of these cells in G1 and M phase. Both the activities of cell cycle arrest and induce apoptosis has proven to be independence by mutations that can cause only one of these affects<ref name='Gonzalez2017'>PMID:28075409</ref>.
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== Disease ==
== Disease ==
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HIV-1 retrovirus is the cause of AIDS disease. HIV-1 is a RNA virus which copy its genome to the host-cell genome in infect cells. HIV-1 infects activated CD4 immune cells and macrophages. When the disease is expressing in carriers, the progressive depletion of CD4 T cells causes immunodeficiency.
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HIV-1 retrovirus is the cause of AIDS disease. HIV-1 is a RNA virus which copy its genome to the host-cell genome in infect cells. HIV-1 infects activated CD4 immune cells and macrophages. When the disease is expressing in carriers, the progressive depletion of CD4 T cells causes immunodeficiency<ref name='Emerman1996'>PMID:8805364</ref>.
For more details about AIDS disease see {{Wikipedia|AIDS}}
For more details about AIDS disease see {{Wikipedia|AIDS}}
For details about another HIV-1 components and its replication pathway see [[HIV and accessory proteins]].
For details about another HIV-1 components and its replication pathway see [[HIV and accessory proteins]].
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== Relevance ==
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Understanding of Vpr structure and molecular mechanism may facilitate the design of HIV-1 antiviral therapy by its inhibition. Deletion of both ''vpr'' and ''vpx'' genes in SIV, which their protein products in SIV combine Vpr function in HIV-1, eliminate virus replication<ref name='Emerman1996'/>. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy <ref name='Gonzalez2017'/>
== Conservation ==
== Conservation ==
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Vpr is highly conserved in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref>PMID:12614620</ref>. In addition, all primate lentiviruses has vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - vpx. In these lentiviruses, vpr and vpx executes together the roles which HIV-1 vpr perform. Vpr and Vpx has low conservation between them.
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Vpr is highly conserved in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates<ref name='Morellet2003'/>. In addition, all primate lentiviruses has vpr gene whose protein product has highly conserved motifs. HIV-2 and SIVsm lentiviruses have additionally gene - vpx. In these lentiviruses, vpr and vpx executes together the roles which HIV-1 vpr perform. Vpr and Vpx has low conservation between them.

Revision as of 23:43, 7 April 2018

HIV-1 Vpr protein (cyan) complex with Human DNA damage-binding protein (grey), VPRBP (pink) and Uracyl-DNA glycosylase (yellow) (PDB code 5jk7)

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3D Structures of Vpr protein

Updated on 07-April-2018

1m8l – Vpr - NMR - HIV-1
1esx - synthetic Vpr - NMR - HIV-1
5jk7 – Vpr + DDB1 + DCAF-1 + UNG2 – X-ray solution - HIV-1
1x9v – Dimeric structure of the Vpr C-terminal domain - NMR
1vpc - C-terminal domain of Vpr - NMR - HIV-1
1fi0 - Vpr residues 13-33 in micelles - NMR - HIV-1
1bde - NMR solution of Vpr peptides connected to cell cycle arrest and nuclear provirus transfer
5b56 - Importin subunit alpha-1 + Vpr C-terminal domain - crystallographic analysis
1kzs, 1kzt, 1kzv - Vpr residues 34-51 - NMR - HIV-1
1dsj - Vpr residues 50-75 - NMR - HIV-1
1ceu - Vpr N-terminal domain - NMR - HIV-1
1dsk - Vpr residues 59-86 - NMR - HIV-1


References

  1. ↑ 1.0 1.1 Morellet N, Bouaziz S, Petitjean P, Roques BP. NMR structure of the HIV-1 regulatory protein VPR. J Mol Biol. 2003 Mar 14;327(1):215-27. PMID:12614620
  2. ↑ 2.0 2.1 Gonzalez ME. The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention. Int J Mol Sci. 2017 Jan 10;18(1). pii: ijms18010126. doi: 10.3390/ijms18010126. PMID:28075409 doi:http://dx.doi.org/10.3390/ijms18010126
  3. ↑ 3.0 3.1 Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol. 1996 Sep 1;6(9):1096-103. PMID:8805364

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Elia Shlush, Michal Harel

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