A novel class of viral Ankyrin proteins targeting the host E3 ubiquitin ligase Cullin-2.

A novel class of viral Ankyrin proteins targeting the host E3 ubiquitin ligase Cullin-2.
J Virol. 2018 Sep 26;:
Authors: Odon V, Georgana I, Holley J, Morata J, Maluquer de Motes C
Abstract
Ankyrin repeat (ANK) domains are one of the most abundant motifs in eukaryotic proteins. ANK proteins are rare amongst viruses with the exception of poxviruses, which presumably acquired them from the host via horizontal gene transfer. The architecture of poxvirus ANK proteins is however different from their cellular counterparts and this precludes a direct acquisition event. Here we combine bioinformatics analysis and quantitative proteomics to discovera new class of viral ANK proteins with a domain organisation that relates to cellular ANK proteins. These non-canonical viral ANK proteins,termed ANK/BC, interact with host Cullin-2 via a C-terminal BCbox resembling that of cellular Cullin-2 substrate adaptors such as the von Hippel-Lindau protein. Mutagenesis of the BC box-like sequence abrogatesbinding to Cullin-2, whereas fusion of this motif to an ANK-only protein confersCullin-2 association. We demonstrate that these viral ANK/BC proteins are potent immunomodulatory proteins suppressing the activation of the pro-inflammatory transcription factors NF-κB and IRF-3 and the production of cytokines and chemokines including interferon, and that association with Cullin-2 is required for optimal inhibitory activity. ANK/BC proteins exist in several o...

Source: Genomics Proteomics ... - September 26, 2018 Category: Genetics & Stem Cells Authors: Odon V, Georgana I, Holley J, Morata J, Maluquer de Motes C Tags: J Virol Source Type: research