Requirement of HIV-1 Vif C-terminus for Vif-CBF-β interaction and assembly of CUL5-containing E3 ligase

Hong Wang, Guoyue Lv, Xiaohong Zhou, Zhaolong Li, Xin Liu, Xiao Fang Yu, Wenyan Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Human immunodeficiency virus type 1 (HIV-1) Vif hijacks an E3 ligase to suppress natural APOBEC3 restriction factors, and core binding factor β (CBF-β) is required for this process. Although an extensive region of Vif spanning most of its N-terminus is known to be critical for binding with CBF-β, involvement of the Vif C-terminus in the interaction with CBF-β has not been fully investigated. Results: Here, through immunoprecipitation analysis of Vif C-terminal truncated mutants of various lengths, we identified that CBF-β binding requires not only certain amino acids (G126A, E134A, Y135A and G138A) in the HCCH region but also the HCCH motif itself, which also affects the Vif-mediated suppression of APOBEC3G/APOBEC3F (A3G/A3F). These mutants still maintained interactions with substrate A3G or A3F as well as other cellular factors ElonginB/C (ELOB/C), indicating that their structures were not functionally affected. Moreover, by determining that the BC box also is necessary for CBF-β interaction in vivo, we speculate that binding to ELOB/C induces conformational changes in Vif, facilitating its interaction with CBF-β and consequent interaction with CUL5. Conclusions: These results provide important information on the assembly of the Vif-CUL5-E3 ubiquitin ligase. Identification of the new binding interface with CBF-β at the C-terminus of HIV-1 Vif also provides novel targets for the development of HIV-1 inhibitors.

Original languageEnglish (US)
Article number290
JournalBMC microbiology
Volume14
Issue number1
DOIs
StatePublished - 2014

Keywords

  • APOBEC3
  • C-terminus
  • CBF-β
  • HIV-1 Vif

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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