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@ARTICLE{Gu:841985,
author = {Gu, Qinyong and Zhang, Zeli and Gertzen, Christoph G. W.
and Häussinger, Dieter and Gohlke, Holger and Münk,
Carsten},
title = {{I}dentification of a {C}onserved {I}nterface of {H}uman
{I}mmunodeficiency {V}irus {T}ype 1 and {F}eline
{I}mmunodeficiency {V}irus {V}ifs with {C}ullin 5},
journal = {Journal of virology},
volume = {92},
number = {6},
issn = {1098-5514},
address = {Baltimore, Md.},
publisher = {Soc.},
reportid = {FZJ-2018-00272},
pages = {e01697-17},
year = {2018},
abstract = {The apolipoprotein B mRNA-editing enzyme, catalytic
polypeptide-like (APOBEC3, A3) family of DNA cytidine
deaminases are intrinsic restriction factors against
retroviruses. In felids such as the domestic cat (Felis
catus), the APOBEC3 (A3) genes encode for the A3Z2s, A3Z3,
and A3Z2Z3 antiviral cytidine deaminases. Only A3Z3 and
A3Z2Z3 inhibit viral infectivity factor (Vif)-deficient
feline immunodeficiency virus (FIV). FIV Vif protein
interacts with Cullin (CUL), Elongin B (ELOB), and Elongin C
(ELOC) to form an E3 ubiquitination complex to induce the
degradation of feline A3s. However, the functional domains
in FIV Vif for interaction with Cullin are poorly
understood. Here, we found that the expression of
dominant-negative CUL5 prevented the degradation of feline
A3s by FIV Vif, while dominant-negative CUL2 had no
influence on the degradation of A3. In
co-immunoprecipitation assays, FIV Vif bound to CUL5 but not
CUL2. To identify the CUL5 interaction site in FIV Vif, the
conserved amino acids from position 47 to 160 of FIV Vif
were mutated, but these mutations did not impair the binding
of Vif to CUL5. By focusing on a potential zinc-binding
motif (K175— C161—C184—C187) of FIV Vif, we found a
conserved hydrophobic region (174IR175) that is important
for CUL5 interaction. Mutating this region also impaired the
FIV Vif-induced degradation of feline A3s. Based on a
structural model of the FIV Vif/CUL5 interaction, residues
52LW53 in CUL5 were identified as mediating the binding to
FIV Vif. By comparing our results to the HIV-1 Vif/CUL5
interaction surface (120IR121, a hydrophobic region that is
localized in the zinc-binding motif), we suggest that the
CUL5 interaction surface in the diverse HIV-1 and FIV Vif is
evolutionarily conserved indicating a strong structural
constraint. However, the FIV Vif/CUL5 interaction is
zinc-independent, which contrasts with the zinc-dependence
of HIV-1 Vif.},
cin = {JSC / NIC / ICS-6},
ddc = {570},
cid = {I:(DE-Juel1)JSC-20090406 / I:(DE-Juel1)NIC-20090406 /
I:(DE-Juel1)ICS-6-20110106},
pnm = {574 - Theory, modelling and simulation (POF3-574) / 553 -
Physical Basis of Diseases (POF3-553) / 511 - Computational
Science and Mathematical Methods (POF3-511)},
pid = {G:(DE-HGF)POF3-574 / G:(DE-HGF)POF3-553 /
G:(DE-HGF)POF3-511},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29263270},
UT = {WOS:000427447100012},
doi = {10.1128/JVI.01697-17},
url = {https://juser.fz-juelich.de/record/841985},
}