Dataset Information

A comparative analysis of the interactomes of viral accessory proteins exploiting DDB1 and Cullin Ubiquitin ligases

ABSTRACT: Viruses have an ambivalent relationship with the host proteome. While several host proteins are indispensable for replication, detrimental restriction factors need to be antagonized. This process is frequently catalysed by viral accessory proteins which exploit the ubiquitin proteasome pathway, DDB1, and Cullin Ubiquitin ligases for the degradation of restriction factors, like in the case of the mouse cytomegalovirus encoded interferon antagonist pM27 which exploits DDB1 for STAT2 degradation. pM27 homologous proteins are conserved in betaherpesviruses. DDB1 and Cullins also serve as essential co-factor for accessory proteins encoded by other virus families like Vpr (HIV-1- and -2-encoded), Vpx (HIV-2-encoded), HBx (HBV-encoded) and its woodchuck hepatitis virus homolog (WHx). To establish a comprehensive understanding of the complexes assembled by viral DDB1-interacting proteins and their targets, we performed immuno-affinity precipitations for a panel of viral proteins known or suspected to interact with DDB1 and/or Cullins. For each protein, we conducted four biological replicates and identified and quantified all co-precipitating proteins by mass spectrometry. Empty plasmids and the HCMV-encoded protein pUL42, which binds the unrelated ubiquitin ligase Itch, served as negative controls and outside group, respectively. This analysis confirmed previously described interactions (pM27 with STAT2), extended known interactions to paralogous proteins (e.g. HBx and WHx with different Spindlin proteins), and documented anticipated interactions for the first time (e.g. Vpr with Bax). The comparison revealed considerable differences concerning the interaction with DDB1 and Cullin 4A/B in terms of the general ability as well as the strength of interaction. On global level, the correlation of the interactomes fitted well with the phylogenetic relationship of the proteins but also highlighted a considerable overlap between the DDB1 interactors of non-related viruses (e.g. herpesviral and hepadnaviral).

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Dominik Andre Meger

LAB HEAD: Dominik A. Megger

PROVIDER: PXD007634 | Pride | 2019-01-14

REPOSITORIES: Pride

ACCESS DATA

Publications

A Mass Spectrometry-Based Profiling of Interactomes of Viral DDB1- and Cullin Ubiquitin Ligase-Binding Proteins Reveals NF-κB Inhibitory Activity of the HIV-2-Encoded Vpx.

Landsberg Christine D CD Megger Dominik A DA Hotter Dominik D Rückborn Meike U MU Eilbrecht Mareike M Rashidi-Alavijeh Jassin J Howe Sebastian S Heinrichs Stefan S Sauter Daniel D Sitek Barbara B Le-Trilling Vu Thuy Khanh VTK Trilling Mirko M

Frontiers in immunology 20181219

Viruses and hosts are situated in a molecular arms race. To avoid morbidity and mortality, hosts evolved antiviral restriction factors. These restriction factors exert selection pressure on the viruses and drive viral evolution toward increasingly efficient immune antagonists. Numerous viruses exploit cellular DNA damage-binding protein 1 (DDB1)-containing Cullin RocA ubiquitin ligases (CRLs) to induce the ubiquitination and subsequent proteasomal degradation of antiviral factors expressed by th ...[more]

PMID: 30619335

Similar Datasets

Project description:Viruses have an ambivalent relationship with the host proteome. While several host proteins are indispensable for replication, detrimental restriction factors need to be antagonized. This process is frequently catalysed by viral accessory proteins which exploit the ubiquitin proteasome pathway, DDB1, and Cullin Ubiquitin ligases for the degradation of restriction factors, like in the case of the mouse cytomegalovirus encoded interferon antagonist pM27 which exploits DDB1 for STAT2 degradation. pM27 homologous proteins are conserved in betaherpesviruses. DDB1 and Cullins also serve as essential co-factor for accessory proteins encoded by other virus families like Vpr (HIV-1- and -2-encoded), Vpx (HIV-2-encoded), HBx (HBV-encoded) and its woodchuck hepatitis virus homolog (WHx). To establish a comprehensive understanding of the complexes assembled by viral DDB1-interacting proteins and their targets, we performed immuno-affinity precipitations for a panel of viral proteins known or suspected to interact with DDB1 and/or Cullins. For each protein, we conducted four biological replicates and identified and quantified all co-precipitating proteins by mass spectrometry. Empty plasmids and the HCMV-encoded protein pUL42, which binds the unrelated ubiquitin ligase Itch, served as negative controls and outside group, respectively. This analysis confirmed previously described interactions (pM27 with STAT2), extended known interactions to paralogous proteins (e.g. HBx and WHx with different Spindlin proteins), and documented anticipated interactions for the first time (e.g. Vpr with Bax). The comparison revealed considerable differences concerning the interaction with DDB1 and Cullin 4A/B in terms of the general ability as well as the strength of interaction. On global level, the correlation of the interactomes fitted well with the phylogenetic relationship of the proteins but also highlighted a considerable overlap between the DDB1 interactors of non-related viruses (e.g. herpesviral and hepadnaviral).

Dataset Information

A comparative analysis of the interactomes of viral accessory proteins exploiting DDB1 and Cullin Ubiquitin ligases

Publications

A Mass Spectrometry-Based Profiling of Interactomes of Viral DDB1- and Cullin Ubiquitin Ligase-Binding Proteins Reveals NF-κB Inhibitory Activity of the HIV-2-Encoded Vpx.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure