PXD053712 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis |
Description | Interferon (IFN)-stimulated gene 15 (ISG15), a ubiquitin-like protein, is covalently conjugated to host immune proteins such as MDA5 and IRF3 in a process called ISGylation, thereby promoting type I interferon (IFN) induction to limit the replication of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, whether SARS-CoV-2 proteins can be directly targeted for ISGylation remains elusive. In this study, we identified the nucleocapsid (N) protein of SARS-CoV-2 as a major substrate of ISGylation catalyzed by the host E3 ligase HERC5; however, N ISGylation is readily removed through de-ISGylation by the papain-like protease (PLpro) activity of NSP3. Mass spectrometry analysis identified that the N protein undergoes ISGylation at four lysine residues (K266, K355, K387 and K388), and mutational analysis of these sites in the context of a SARS-CoV-2 replicon (N-4KR) abolished N ISGylation and alleviated ISGylation-mediated inhibition of viral RNA synthesis. Furthermore, our results indicated that HERC5 targets preferentially phosphorylated N protein for ISGylation to regulate its oligomeric assembly. These findings reveal a novel mechanism by which the host ISGylation machinery directly targets SARS-CoV-2 proteins to restrict viral replication and illuminate how an intricate interplay of host (HERC5) and viral (PLpro) enzymes coordinates viral protein ISGylation and thereby regulates virus replication. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:54:53.708.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD053712 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Junji Zhu |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: 2697049; |
ModificationList | ubiquitination signature dipeptidyl lysine; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-07-06 09:55:52 | ID requested | |
1 | 2024-08-14 02:33:23 | announced | |
⏵ 2 | 2024-10-22 06:54:54 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: SARS-CoV-2 |
N protein |
ISG15 |
ISGylation |
HERC5 |
papain-like protease |
Contact List
Michaela Gack |
contact affiliation | Florida Research and Innovation Center, Cleveland Clinic |
contact email | GACKM@ccf.org |
lab head | |
Junji Zhu |
contact affiliation | Florida Research and innovation center, Cleveland Clinic |
contact email | ZHUJ6@ccf.org |
dataset submitter | |
Full Dataset Link List
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/2024/08/PXD053712 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD053712
- Label: PRIDE project
- Name: ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis