Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif.

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.
Mesh Terms:
Amino Acid Sequence, Core Binding Factor Alpha 2 Subunit, Core Binding Factor beta Subunit, Crystallography, X-Ray, Cullin Proteins, Humans, Models, Molecular, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Protein Stability, Protein Structure, Tertiary, Suppressor of Cytokine Signaling Proteins, Transcription Factors, vif Gene Products, Human Immunodeficiency Virus
Nature
Date: Jan. 09, 2014
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