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Trends Biochem Sci. 2014 Sep;39(9):373-80. doi: 10.1016/j.tibs.2014.07.001. Epub 2014 Aug 12.

Structural insights for HIV-1 therapeutic strategies targeting Vif.

Author information

1
OyaGen, Inc, 77 Ridgeland Road, Rochester, NY 14623, USA.
2
Cogent Professionals, 101 West Ohio Street, Suite 2000, Indianapolis, IN 46204, USA.
3
OyaGen, Inc, 77 Ridgeland Road, Rochester, NY 14623, USA; University of Rochester, School of Medicine and Dentistry, Department of Biochemistry and Biophysics, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: hsmith@oyageninc.com.

Abstract

HIV-1 viral infectivity factor (Vif) is a viral accessory protein that is required for HIV-1 infection due largely to its role in recruiting antiretroviral factors of the APOBEC3 (apolipoprotein B editing catalytic subunit-like 3) family to an E3 ubiquitin ligase complex for polyubiquitylation and proteasomal degradation. The crystal structure of the (near) full-length Vif protein in complex with Elongin (Elo)B/C, core-binding factor (CBF)β and Cullin (Cul)5 revealed that Vif has a novel structural fold. In our opinion the structural data revealed not only the protein-protein interaction sites that determine Vif stability and interaction with cellular proteins, but also motifs driving Vif homodimerization, which are essential in Vif functionality and HIV-1 infection. Vif-mediated protein-protein interactions are excellent targets for a new class of antiretroviral therapeutics to combat AIDS.

KEYWORDS:

APOBEC; Elongin B/C; core-binding factor β; cullin 5; viral infectivity factor

PMID:
25124760
PMCID:
PMC4511815
DOI:
10.1016/j.tibs.2014.07.001
[Indexed for MEDLINE]
Free PMC Article

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