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Vpr protein

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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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1 Function
2 Disease
3 Relevance
4 Conservation

Function

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 (AIDS) disease, including regulation the HIV-1 pre-integration complex (PIC) nuclear import and virus replication in non-dividing macrophages^[1]. 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^[2].

Disease

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^[3]. For more details about AIDS disease see AIDS in Wikipedia

For details about another HIV-1 components and its replication pathway see HIV and accessory proteins.

Relevance

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^[3]. The multiple significant functions that Vpr fills in HIV-1 replication makes it an attractive candidate for antiviral therapy ^[2]

Conservation

Vpr is highly conserved in HIV and simian immunodeficiency virus (SIV), similar retrovirus which infects non-human primates^[1]. 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.

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

↑ ^1.0 ^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
↑ ^2.0 ^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
↑ ^3.0 ^3.1 Emerman M. HIV-1, Vpr and the cell cycle. Curr Biol. 1996 Sep 1;6(9):1096-103. PMID:8805364