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| The interactions between VprBP and Vpr are located in a cleft formed by VprBD canonical WD40 seven-blade β-propeller which is lined by acidic residues on one end and hydrophobic residues at the center. The interactions are formed by hydrogen bonds, Vpr Phe residue buried in VprBP hydrophobic pocket and VprBP Trp binding to residues in Vpr pocket<ref>PMID:27571178</ref>. | | The interactions between VprBP and Vpr are located in a cleft formed by VprBD canonical WD40 seven-blade β-propeller which is lined by acidic residues on one end and hydrophobic residues at the center. The interactions are formed by hydrogen bonds, Vpr Phe residue buried in VprBP hydrophobic pocket and VprBP Trp binding to residues in Vpr pocket<ref>PMID:27571178</ref>. |
| </StructureSection> | | </StructureSection> |
| == 3D Structures of VPRBP == | | == 3D Structures of VprBP == |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} | | Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}} |
Revision as of 09:07, 19 December 2017
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Function
VprBP (VPR-binding protein) is a HIV-1 WD40 protein is essential for DNA replication and embryonic development[1]. VprBP has intrinsic kinase activity and is capable of phosphorylating histone H2A. Recruitment of VprBP by Vpr is essential for HIV-1 VPR activity of initiating the host cell response cycle arresting its G(2) phase following mitosis[2]. VprBP interacts with merlin which is then recruited to the E3 ligase complex resulting in its polyubiquitination and consequently its proteasome-mediated degradation[3].
Relevance
VprBP inhibition could be a strategy for the development of anticancer therapeutics[4].
Structural highlights
The interactions between VprBP and Vpr are located in a cleft formed by VprBD canonical WD40 seven-blade β-propeller which is lined by acidic residues on one end and hydrophobic residues at the center. The interactions are formed by hydrogen bonds, Vpr Phe residue buried in VprBP hydrophobic pocket and VprBP Trp binding to residues in Vpr pocket[5].
- ↑ McCall CM, Miliani de Marval PL, Chastain PD 2nd, Jackson SC, He YJ, Kotake Y, Cook JG, Xiong Y. Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development. Mol Cell Biol. 2008 Sep;28(18):5621-33. doi: 10.1128/MCB.00232-08. Epub 2008 Jul , 7. PMID:18606781 doi:https://dx.doi.org/10.1128/MCB.00232-08
- ↑ Le Rouzic E, Belaidouni N, Estrabaud E, Morel M, Rain JC, Transy C, Margottin-Goguet F. HIV1 Vpr arrests the cell cycle by recruiting DCAF1/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase. Cell Cycle. 2007 Jan 15;6(2):182-8. Epub 2007 Jan 17. PMID:17314515
- ↑ Huang J, Chen J. VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation. Oncogene. 2008 Jul 3;27(29):4056-64. Epub 2008 Mar 10. PMID:18332868 doi:onc200844
- ↑ Kim K, Kim JM, Kim JS, Choi J, Lee YS, Neamati N, Song JS, Heo K, An W. VprBP has intrinsic kinase activity targeting histone H2A and represses gene transcription. Mol Cell. 2013 Nov 7;52(3):459-67. doi: 10.1016/j.molcel.2013.09.017. Epub 2013, Oct 17. PMID:24140421 doi:https://dx.doi.org/10.1016/j.molcel.2013.09.017
- ↑ Wu Y, Zhou X, Barnes CO, DeLucia M, Cohen AE, Gronenborn AM, Ahn J, Calero G. The DDB1-DCAF1-Vpr-UNG2 crystal structure reveals how HIV-1 Vpr steers human UNG2 toward destruction. Nat Struct Mol Biol. 2016 Aug 29. doi: 10.1038/nsmb.3284. PMID:27571178 doi:https://dx.doi.org/10.1038/nsmb.3284
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3D Structures of VprBP
Updated on 19-December-2017
4pxw – hVprBP residues 1039-1401 (mutant) - human
3wa0 – hVprBP residues 1417-1506 + merlin
4p7i – hVprBP residues 998-1058 + merlin
4z8l, 5aja, 4cc9 – hVprBP residues 1057-1396 + VPX + SAMHD1
5jk7 – hVprBP residues 1045-1396 + Vpr + DNA damage-binding protein + uracil-DNA glycosylase
References
