title: Requirement of HIV-1 Vif C-terminus for Vif-CBF-β interaction and assembly of CUL5-containing E3 ligase.
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.
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. wanghong309768094@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. lgy08@sina.com.
authors.forename: Guoyue
authors.initials: G
authors.lastname: Lv
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. 21632709@qq.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. lzl19880514@126.com.
authors.forename: Zhaolong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. liuxin87529524@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. xyu2@jhu.edu.|Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, USA. xyu2@jhu.edu.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Yu
authors.affiliation: Institute of Virology and AIDS Research, First Hospital of Jilin University, No 519. East Minzhu Avenue, Changchun, Jilin Province, China. zhangwenyan@jlu.edu.cn.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Zhang
mesh_terms: D050658:Core Binding Factor beta Subunit / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: C496871:CUL5 protein, human; D050658:Core Binding Factor beta Subunit; D044842:Cullin Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D044767:Ubiquitin-Protein Ligases