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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.
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
Shin D, Mukherjee R, Grewe D, Bojkova D, Baek K, Bhattacharya A, Schulz L, Widera M, Mehdipour AR, Tascher G, Geurink PP, Wilhelm A, van der Heden van Noort GJ, Ovaa H, M, ΓΌ, ller S, Knobeloch KP, Rajalingam K, Schulman BA, Cinatl J, Hummer G, Ciesek S, Dikic I, Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity. Nature, 587(7835):657-662(2020) [pubmed]
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
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Dataset FTP location
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