Reported by: School of Life Science and Technology
Translated by: SUN Jian
Edited by: Jennifer Taylor
9 January 2014 an article titled “Structural basis for hijacking CBF-β and CUL5 E3 ligase complex by HIV-1 Vif” was published in the last Nature journal. It was written by HIT Professor HUANG Zhiwei’s research team and introduced by Stéphane Larochelle, the vice-editor of Nature Structural and Molecular Biology in the Research Highlight section of the journal. Professor HUANG Zhiwei is a professor in the School of Life Science and Technology and the director of the Structure and Molecular Biology Laboratory. His team members include HIT students from the laboratory GUO Yingying, DONG Liyong, QIU Xiaolin, WANG Yishu, ZHANG Bailing, LIU Hongnan, YU You, ZHANG Yi and YANG Maojun.
In their research, the human immunodeficiency virus (HIV)-1 protein Vif has a central role in the neutralization of host innate defenses by hijacking cellular proteasomal degradation pathways to subvert the antiviral activity of host restriction factors. However, the underlying mechanism by which Vif achieves this remained unclear. They reported the 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. The unique zinc-finger motif of Vif, which is located between the two Vif domains, makes no contact with the other proteins but stabilizes the conformation of the α-domain., which may be important for Vif–CUL5 interaction. Together, their data reveals the structural basis for Vif hijacking of the CBF-β and CUL5 E3 ligase complex, laying a foundation for the future rational design of novel anti-HIV drugs.
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