PXD053924-2

PXD053924 is an original dataset announced via ProteomeXchange.

Title	Identification of interactors with HCMV pTRS1 using BioID and proteomics
Description	Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects the majority of the world’s population. Lytic HCMV replication in immunocompromised individuals or neonates can lead to severe disease in multiple organ systems and even death. The establishment of lytic replication is driven by the first viral proteins expressed upon infection, the immediate early proteins, which play a key role in creating an intracellular environment conducive to virus replication. Two immediate early proteins, the functional orthologs pTRS1 and pIRS1, stimulate immediate early gene expression by suppressing antiviral PKR/eIF2a signaling and enhance the translation of viral mRNAs independent of PKR antagonism. To better understand the molecular functions of pTRS1, we used proximity labeling proteomics to identify proteins that interact with pTRS1 in infected cells. Multiple novel host and viral interactors were identified, including the catalytic subunits of the protein phosphatase 1 (PP1) holoenzyme. Mutations to a PP1 catalytic subunit known to disrupt binding to PP1 regulatory subunits decreased binding to pTRS1. pTRS1 immune complexes contained phosphatase activity, and inhibition of phosphatase activity in transfected or infected cells reversed the ability of pTRS1 to inhibit the antiviral kinase PKR. Depletion of individual PP1 catalytic subunits decreased virus replication and increased the phosphorylation of the PKR substrate eIF2a. Together our data suggest potential novel functions for pTRS1, and define a novel role for PP1 as an antagonist of the antiviral PKR/eIF2 signaling axis during HCMV infection.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_07:01:26.631.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Erik Lenarcic
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-12 13:23:42	ID requested
1	2024-10-11 09:49:57	announced
⏵ 2	2024-10-22 07:01:27	announced	2024-10-22: Updated project metadata.

10.1128/JVI.00590-24;

submitter keyword: Human, human herpesvirus, virology, label-free quantitation, BioID

Nathaniel Moorman
contact affiliation	Department of Microbiology and Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
contact email	nathaniel_moorman@med.unc.edu
lab head
Erik Lenarcic
contact affiliation	UNC Chapel Hill School of Medicine Department of Microbiology and Immunology
contact email	erik_lenarcic@med.unc.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/10/PXD053924

PRIDE project URI

• PRIDE
  1. PXD053924
     1. Label: PRIDE project
     2. Name: Identification of interactors with HCMV pTRS1 using BioID and proteomics