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PXD018983-1

PXD018983 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCoronavirus PLPro interactome AP-MS data
DescriptionMain proteases and papain-like proteases (PLpro) are essential coronaviral enzymes required for polypeptide processing during viral maturation. PLpro additionally cleave host cellular proteins to evade anti-viral immune responses. Here, we provide biochemical, structural and functional characterizations of PLpro from SARS-Cov-2 (PLproCoV2) and reveal differences to that of SARS (PLproSARS) in controlling interferon (IFN) and NF-kB pathways. PLproCoV2 and PLproSARS share 89% sequence similarity, yet they differ in their substrate preferences: PLproCoV2 cleaves predominantly ISG15, while PLproSARS targets preferentially ubiquitin chains and Nedd8. The crystal structure of PLproCoV2 in complex with the full-size ISG15 revealed the secondary binding site for the amino-terminal domain of ISG15, thus explaining the affinity and higher specificity, as well as indicating a role for the tyrosine 268 in positioning GRL-0617 inhibitor of PLproCoV2. In human cells, PLproCoV2 cleaves ISG15 from interferon responsive factor 3 (IRF3), blocks its nuclear translocation and reduces type I interferon responses, whereas PLproSARS preferentially mediates deubiquitination and deneddylation of critical components of the NF-kB pathway. Inhibition of PLproCoV2 by GRL-0617 blocks virus-induced cytopathogenic effect, reduces viral release from infected cells and fosters the anti-viral interferon pathway upon infection with SARS-CoV-2. We propose that therapeutic targeting of PLproCoV2 can inhibit SARS-CoV-2 infection and promote anti-viral immunity.
HostingRepositoryPRIDE
AnnounceDate2020-08-05
AnnouncementXMLSubmission_2020-08-05_10:10:52.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGeorg Tascher
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-04 18:11:31ID requested
12020-08-05 10:10:53announced
22020-10-01 23:14:52announced2020-10-02: Updated publication reference for PubMed record(s): 32726803.
Publication List
Dataset with its publication pending
Keyword List
ProteomeXchange project tag: Sars-cov-2, Covid-19
submitter keyword: SARS-CoV-2, PLPro, ISGylation, AP-MS
Contact List
Ivan Dikic
contact affiliationInstitute of Biochemistry II, Faculty of Medicine, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
contact emaildikic@biochem2.uni-frankfurt.de
lab head
Georg Tascher
contact affiliationInstitute of Biochemistry II, Goethe University Hospital Frankfurt/Main, Germany
contact emailtascher@med.uni-frankfurt.de
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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