title: Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif.
abstract: The human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defences by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors; however, the underlying mechanism by which Vif achieves this remains unclear. Here we report a crystal structure of the Vif-CBF-β-CUL5-ELOB-ELOC complex. The structure reveals that Vif, by means of two domains, organizes formation of the pentameric complex by interacting with CBF-β, CUL5 and ELOC. The larger domain (α/β domain) of Vif binds to the same side of CBF-β as RUNX1, indicating that Vif and RUNX1 are exclusive for CBF-β binding. Interactions of the smaller domain (α-domain) of Vif with ELOC and CUL5 are cooperative and mimic those of SOCS2 with the latter two proteins. A unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contacts with the other proteins but stabilizes the conformation of the α-domain, which may be important for Vif-CUL5 interaction. Together, our data reveal the structural basis for Vif hijacking of the CBF-β and CUL5 E3 ligase complex, laying a foundation for rational design of novel anti-HIV drugs.
authors.affiliation: 1] School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China [2].
authors.forename: Yingying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: 1] School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China [2].
authors.forename: Liyong
authors.initials: L
authors.lastname: Dong
authors.affiliation: 1] School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China [2].
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Qiu
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Yishu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Bailing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Hongnan
authors.initials: H
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: You
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zang
authors.affiliation: MOE Key Laboratory of Protein Sciences, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin 150080, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D050676:Core Binding Factor Alpha 2 Subunit / Q000378:metabolism; D050658:Core Binding Factor beta Subunit / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D044842:Cullin Proteins / Q000737:chemistry* / Q000378:metabolism*; D000075065:Elongin; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C493692:CBFB protein, human; C496871:CUL5 protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D050658:Core Binding Factor beta Subunit; D044842:Cullin Proteins; C000616396:ELOB protein, human; C000616395:ELOC protein, human; D000075065:Elongin; D046912:Multiprotein Complexes; C493728:RUNX1 protein, human; C106643:SOCS2 protein, human; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1