PXD018983-1

PXD018983 is an original dataset announced via ProteomeXchange.

Title	Coronavirus PLPro interactome AP-MS data
Description	Main 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.
HostingRepository	PRIDE
AnnounceDate	2020-08-05
AnnouncementXML	Submission_2020-08-05_10:10:52.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georg Tascher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-04 18:11:31	ID requested
⏵ 1	2020-08-05 10:10:53	announced
2	2020-10-01 23:14:52	announced	2020-10-02: Updated publication reference for PubMed record(s): 32726803.
3	2024-10-22 05:10:21	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: SARS-CoV-2, PLPro, ISGylation, AP-MS

Ivan Dikic
contact affiliation	Institute of Biochemistry II, Faculty of Medicine, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
contact email	dikic@biochem2.uni-frankfurt.de
lab head
Georg Tascher
contact affiliation	Institute of Biochemistry II, Goethe University Hospital Frankfurt/Main, Germany
contact email	tascher@med.uni-frankfurt.de
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/2020/08/PXD018983

PRIDE project URI

• PRIDE
  1. PXD018983
     1. Label: PRIDE project
     2. Name: Coronavirus PLPro interactome AP-MS data