Vpr protein: Difference between revisions

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=== Vpr induce cell cycle arrest by recruits cellular targets for degradation<ref name='Wu2016'>PMID:27571178</ref> ===

One phenotype of Vpr expression is the induction of cell cycle arrest in G2 phase. This arrest executes by engaging of damage–binding protein 1 (DDB1) and CUL4A-associated factor 1 (DCAF1) to Vpr. DCAF1 is a substrate receptor of the Cullin4–RING E3 ubiquitin ligase (CRL4) of the host ubiquitin–proteasome-mediated protein degradation pathway. Mutations in Vpr that abolish its interaction with DCAF1, or silencing of DCAF1, eliminate cell-cycle arrest. The crystal structure of <scene name='75/750237/Vpr_ddb1_dcaf1_ung2/2'>DDB1–DCAF1–HIV-1–Vpr–uracil-DNA glycosylase (UNG2) complex</scene> elucidate the molecular mechanism in which Vpr inhibits UNG2 enzymatic activity and send it for degradation:

DCAF1 WD40 domain <scene name='75/750237/Dcaf1_vpr/1'>binds to Vpr</scene> by its N-terminus and α3 helix. In addition, DCAF1 is anchored into DDB1 by a helix-loop-helix motif. These motifs are commonly found in substrate receptor proteins that bind to DDB1. Finally, Vpr uses structural mimicry to DNA to <scene name='75/750237/~~Dcaf1_ung2~~/1'>engages UNG2</scene>. It interacts with UNG2 by residues in the hydrophobic cleft and an insert loop (residues 266–283), which mimics the phosphate backbone in the DNA. When interacts with DNA, UNG2 Leu272 residue uses to insert into the minor groove. The importance of Leu272 residue to UNG2-Vpr interaction was demonstrated by mutagenesis. Thus, Vpr recruite the CRL4–DCAF1 E3 ubiquitin ligase and targets cellular substrates for degradation. The reason for UNG2 degradation is not clear yet. However, their is a possibility that UNG2 exerts a negative effect on HIV-1 replication.

DCAF1 WD40 domain <scene name='75/750237/Dcaf1_vpr/1'>binds to Vpr</scene> by its N-terminus and α3 helix. In addition, DCAF1 is anchored into DDB1 by a helix-loop-helix motif. These motifs are commonly found in substrate receptor proteins that bind to DDB1. Finally, Vpr uses structural mimicry to DNA to <scene name='75/750237/Vpr_ung2/1'>engages UNG2</scene>. It interacts with UNG2 by residues in the hydrophobic cleft and an insert loop (residues 266–283), which mimics the phosphate backbone in the DNA. When interacts with DNA, UNG2 Leu272 residue uses to insert into the minor groove. The importance of Leu272 residue to UNG2-Vpr interaction was demonstrated by mutagenesis. Thus, Vpr recruite the CRL4–DCAF1 E3 ubiquitin ligase and targets cellular substrates for degradation. The reason for UNG2 degradation is not clear yet. However, their is a possibility that UNG2 exerts a negative effect on HIV-1 replication.

== Disease ==

Vpr protein: Difference between revisions

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 === Vpr induce cell cycle arrest by recruits cellular targets for degradation<ref name='Wu2016'>PMID:27571178</ref> ===
 One phenotype of Vpr expression is the induction of cell cycle arrest in G2 phase. This arrest executes by engaging of damage–binding protein 1 (DDB1) and CUL4A-associated factor 1 (DCAF1) to Vpr. DCAF1 is a substrate receptor of the Cullin4–RING E3 ubiquitin ligase (CRL4) of the host ubiquitin–proteasome-mediated protein degradation pathway. Mutations in Vpr that abolish its interaction with DCAF1, or silencing of DCAF1, eliminate cell-cycle arrest. The crystal structure of <scene name='75/750237/Vpr_ddb1_dcaf1_ung2/2'>DDB1–DCAF1–HIV-1–Vpr–uracil-DNA glycosylase (UNG2) complex</scene> elucidate the molecular mechanism in which Vpr inhibits UNG2 enzymatic activity and send it for degradation:
-DCAF1 WD40 domain <scene name='75/750237/Dcaf1_vpr/1'>binds to Vpr</scene> by its N-terminus and α3 helix. In addition, DCAF1 is anchored into DDB1 by a helix-loop-helix motif. These motifs are commonly found in substrate receptor proteins that bind to DDB1. Finally, Vpr uses structural mimicry to DNA to <scene name='75/750237/Dcaf1_ung2/1'>engages UNG2</scene>. It interacts with UNG2 by residues in the hydrophobic cleft and an insert loop (residues 266–283), which mimics the phosphate backbone in the DNA. When interacts with DNA, UNG2 Leu272 residue uses to insert into the minor groove. The importance of Leu272 residue to UNG2-Vpr interaction was demonstrated by mutagenesis. Thus, Vpr recruite the CRL4–DCAF1 E3 ubiquitin ligase and targets cellular substrates for degradation. The reason for UNG2 degradation is not clear yet. However, their is a possibility that UNG2 exerts a negative effect on HIV-1 replication.
+DCAF1 WD40 domain <scene name='75/750237/Dcaf1_vpr/1'>binds to Vpr</scene> by its N-terminus and α3 helix. In addition, DCAF1 is anchored into DDB1 by a helix-loop-helix motif. These motifs are commonly found in substrate receptor proteins that bind to DDB1. Finally, Vpr uses structural mimicry to DNA to <scene name='75/750237/Vpr_ung2/1'>engages UNG2</scene>. It interacts with UNG2 by residues in the hydrophobic cleft and an insert loop (residues 266–283), which mimics the phosphate backbone in the DNA. When interacts with DNA, UNG2 Leu272 residue uses to insert into the minor groove. The importance of Leu272 residue to UNG2-Vpr interaction was demonstrated by mutagenesis. Thus, Vpr recruite the CRL4–DCAF1 E3 ubiquitin ligase and targets cellular substrates for degradation. The reason for UNG2 degradation is not clear yet. However, their is a possibility that UNG2 exerts a negative effect on HIV-1 replication.
 == Disease ==