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




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BMC Microbiology

, 14:290

Microbe-host interactions and microbial pathogenicity

Abstract

BackgroundHuman 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.

ResultsHere, 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.

ConclusionsThese 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.

KeywordsHIV-1 Vif CBF-β C-terminus APOBEC3 Electronic supplementary materialThe online version of this article doi:10.1186-s12866-014-0290-7 contains supplementary material, which is available to authorized users.

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Autor: Hong Wang - Guoyue Lv - Xiaohong Zhou - Zhaolong Li - Xin Liu - Xiao-Fang Yu - Wenyan Zhang

Fuente: https://link.springer.com/



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