Title |
Requirement of HIV-1 Vif C-terminus for Vif-CBF-β interaction and assembly of CUL5-containing E3 ligase
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Published in |
BMC Microbiology, November 2014
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DOI | 10.1186/s12866-014-0290-7 |
Pubmed ID | |
Authors |
Hong Wang, Guoyue Lv, Xiaohong Zhou, Zhaolong Li, Xin Liu, Xiao-Fang Yu, Wenyan Zhang |
Abstract |
BackgroundHuman immunodeficiency virus type 1 (HIV-1) Vif hijacks an E3 ligase to suppress natural APOBEC3 restriction factors, and core binding factor ß (CBF-ß) 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-ß, involvement of the Vif C-terminus in the interaction with CBF-ß has not been fully investigated.ResultsHere, through immunoprecipitation analysis of Vif C-terminally truncated mutants of various lengths, we identified that CBF-ß 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-ß interaction in vivo, we speculate that binding to ELOB/C induces conformational changes in Vif, facilitating its interaction with CBF-ß and consequent interaction with CUL5.ConclusionsThese results provide important information on the assembly of the Vif-CUL5-E3 ubiquitin ligase. Identification of the new binding interface with CBF-ß at the C-terminus of HIV-1 Vif also provides novel targets for the development of HIV-1 inhibitors. |
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