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PXD030530

PXD030530 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein
DescriptionSARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.
HostingRepositoryMassIVE
AnnounceDate2021-12-19
AnnouncementXMLSubmission_2021-12-19_16:27:07.906.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterBirgit Schilling
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: SARS coronavirus; NCBI TaxID: 227859;
ModificationListSuccinyl
InstrumentTripleTOF 6600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-12-19 16:13:42ID requested
12021-12-19 16:27:08announced
Publication List
no publication
Keyword List
submitter keyword: sirtuin 5, succinylation, NSP14, SARS-CoV-2
Contact List
Birgit Schilling
contact affiliationBuck Institute
contact emailbschilling@buckinstitute.org
lab head
Birgit Schilling
contact affiliationBuck Institute
contact emailbschilling@buckinstitute.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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