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PXD069398-1

PXD069398 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleInteractomics of SARS-CoV-2 Macrodomain 1 Reveals Putative Clients of ADP-ribosyl Hydrolase Activity
DescriptionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has greatly impacted public health due to high rates of transmissibility and mutation during the COVID-19 pandemic. Macrodomain 1 (Mac1) of non-structural protein 3 remained well-conserved across variants and is critical for suppression of host immune response to infection, making Mac1 a promising target for therapeutic development. Mac1 binds and cleaves the post-translational modification ADP-ribose and is hypothesized to have a downstream effect on host interferon response, but the exact cellular targets of Mac1 are still unknown. Characterizing the substrates of Mac1 ADP-ribosyl hydrolase activity using a catalytically inactive mutant N40D can reveal critical virus-host interactions to identify protein targets of Mac1 and reveal mechanisms of host interferon suppression. Here, we co-immunoprecipitated WT Mac1 and Mac1 N40D from HEK293T and A549 cell lines and quantified changes in protein interactions by TMT-multiplexed tandem mass spectrometry. We identified interactions between Mac1 and ADP-ribosylated substrates involved in DNA damage response, cytoskeletal components, and cell cycle regulation. Additionally, several members of the TRiC complex involved in protein folding were selectively enriched with mutant Mac1 from A549 cells. These findings suggest a novel role of Mac1 in regulating host protein folding.
HostingRepositoryPRIDE
AnnounceDate2026-05-22
AnnouncementXMLSubmission_2026-05-22_07:58:56.860.xml
DigitalObjectIdentifierhttps://doi.org/10.6019/PXD069398
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterCrissey Cameron
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-10-13 08:01:25ID requested
12026-05-22 07:58:57announced
Publication List
10.6019/PXD069398;
10.3390/V18060587;
Keyword List
submitter keyword: ADP-ribose, Macrodomain 1, affinity purification-mass spectrometry, Virus-host protein interactions, SARS-CoV-2, Interactomics
Contact List
Lars Plate
contact affiliationDepartments of Chemistry, Biological Sciences, Vanderbilt University and Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center
contact emaillars.plate@vanderbilt.edu
lab head
Crissey Cameron
contact affiliationVanderbilt University
contact emailcrissey.d.cameron@vanderbilt.edu
dataset submitter
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Dataset FTP location
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