Description: Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

This title appears in the Scientific Report : 2018

Identification of a Conserved Interface of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Vifs with Cullin 5

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 cytid...

Personal Name(s):	Gu, Qinyong
	Zhang, Zeli / Gertzen, Christoph G. W. / Häussinger, Dieter / Gohlke, Holger / Münk, Carsten (Corresponding author)
Contributing Institute:	Strukturbiochemie; ICS-6 John von Neumann - Institut für Computing; NIC Jülich Supercomputing Center; JSC
Published in:	Journal of virology, 92 (2018) 6, S. e01697-17
Imprint:	Baltimore, Md. Soc. 2018
PubMed ID:	29263270
DOI:	10.1128/JVI.01697-17
Document Type:	Journal Article
Research Program:	Computational Science and Mathematical Methods Physical Basis of Diseases Theory, modelling and simulation
Link:	Published on 2017-12-20. Available in OpenAccess from 2018-06-20. Restricted Restricted Published on 2017-12-20. Available in OpenAccess from 2018-06-20.
	Publikationsportal JuSER

Please use the identifier: http://hdl.handle.net/2128/17713 in citations.
Please use the identifier: http://dx.doi.org/10.1128/JVI.01697-17 in citations.

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.