Journal
FASEB JOURNAL
Volume 21, Issue 1, Pages 217-222Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.06-6773com
Keywords
HIV-1 virion; lentiviral Vif proteins; TPEN; zinc binding motif
Categories
Funding
- PHS HHS [A1062644] Funding Source: Medline
Ask authors/readers for more resources
APOBEC3 proteins are cellular antiviral proteins that are targeted for proteasomal degradation by primate lentiviral Vif proteins. Vif acts as a substrate receptor for the Cullin5 (Cul5) E3 ubiquitin ligase, specifically interacting with Cul5 through a novel H-(x5)-C-(x17-18)-C-(x3-5)-H zinc binding motif. Using the membranepermeable zinc chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl) ethylenediamine ( TPEN), we demonstrated a requirement for zinc for Vif function in vivo. Treatment with TPEN at an IC50 of 1.79 mu M inhibits Cul5 recruitment and APOBEC3G (A3G) degradation. Zinc chelation prevented Vif function in infectivity assays, allowing the virus to become sensitive to the antiviral activity of A3G. Zinc chelation had no effect on cellular Cul5-SOCS3 E3 ligase assembly, suggesting that zinc-dependent E3 ligase assembly may be unique to HIV-1 Vif, representing a new target for novel drug design.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available