Unknown

Dataset Information

0

HIV-1 Vpr protein directly loads helicase-like transcription factor (HLTF) onto the CRL4-DCAF1 E3 ubiquitin ligase.


ABSTRACT: The viral protein R (Vpr) is an accessory virulence factor of HIV-1 that facilitates infection in immune cells. Cellular functions of Vpr are tied to its interaction with DCAF1, a substrate receptor component of the CRL4 E3 ubiquitin ligase. Recent proteomic approaches suggested that Vpr degrades helicase-like transcription factor (HLTF) DNA helicase in a proteasome-dependent manner by redirecting the CRL4-DCAF1 E3 ligase. However, the precise molecular mechanism of Vpr-dependent HLTF depletion is not known. Here, using in vitro reconstitution assays, we show that Vpr mediates polyubiquitination of HLTF, by directly loading it onto the C-terminal WD40 domain of DCAF1 in complex with the CRL4 E3 ubiquitin ligase. Mutational analyses suggest that Vpr interacts with DNA-binding residues in the N-terminal HIRAN domain of HLTF in a manner similar to the recruitment of another target, uracil DNA glycosylase (UNG2), to the CRL4-DCAF1 E3 by Vpr. Strikingly, Vpr also engages a second, adjacent region, which connects the HIRAN and ATPase/helicase domains. Thus, our findings reveal that Vpr utilizes common as well as distinctive interfaces to recruit multiple postreplication DNA repair proteins to the CRL4-DCAF1 E3 ligase for ubiquitin-dependent proteasomal degradation.

SUBMITTER: Zhou X 

PROVIDER: S-EPMC5743084 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

HIV-1 Vpr protein directly loads helicase-like transcription factor (HLTF) onto the CRL4-DCAF1 E3 ubiquitin ligase.

Zhou Xiaohong X   DeLucia Maria M   Hao Caili C   Hrecka Kasia K   Monnie Christina C   Skowronski Jacek J   Ahn Jinwoo J  

The Journal of biological chemistry 20171027 51


The viral protein R (Vpr) is an accessory virulence factor of HIV-1 that facilitates infection in immune cells. Cellular functions of Vpr are tied to its interaction with DCAF1, a substrate receptor component of the CRL4 E3 ubiquitin ligase. Recent proteomic approaches suggested that Vpr degrades helicase-like transcription factor (HLTF) DNA helicase in a proteasome-dependent manner by redirecting the CRL4-DCAF1 E3 ligase. However, the precise molecular mechanism of Vpr-dependent HLTF depletion  ...[more]

Similar Datasets

| S-EPMC7923639 | biostudies-literature
| S-EPMC5391453 | biostudies-literature
| S-EPMC4058697 | biostudies-literature
| S-EPMC3955192 | biostudies-literature
| S-EPMC2828953 | biostudies-literature
| S-EPMC4557334 | biostudies-literature
| S-EPMC6071318 | biostudies-literature
| S-EPMC10942865 | biostudies-literature
| S-EPMC3182024 | biostudies-literature
| S-EPMC8591539 | biostudies-literature