PXD018346 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mapping of ISG15 interaction partners by GST pull down coupled to mass spectrometry |
Description | During infection, interferon production leads to upregulation of the interferon-stimulated gene 15 (ISG15) which encodes the ubiquitin-like protein ISG15. ISG15 has a profound role in restricting intracellular infection by viral and bacterial pathogens. It can exert its function either as a free intracellular or extracellular molecule, or as an ubiquitin-like conjugate to substrate proteins in a process called ISGylation. Here, we used a viral-like particle trapping (Virotrap) technology and GST pull down, both coupled to mass spectrometry, to screen for intracellular ISG15-binding proteins. As strongest hit, we identified RNF213, a very large interferon-induced protein targeted to lipid droplets and a genetic risk factor for Moyamoya disease, a rare cerebrovascular disorder. We verified binding of ISG15 and RNF213 with biochemical methods and imaging and found that interferon signaling induces ISGylation and oligomerization of RNF213 on the surface of lipid droplets, acting as a binding platform for ISGylated proteins. Moreover, we showed that knockdown of RNF213 promotes in vitro infection by Listeria monocytogenes, respiratory syncytial virus (RSV) and Coxsackie virus (CV) B3, suggesting a broad antimicrobial activity of RNF213. In contrast, overexpression of RNF213 restricted Listeria infection and was associated with a striking co-localization of RNF213 with intracellular bacteria. Infection experiments in RNF213 deficient mice corroborated these results in vivo, revealing a so far unknown function of RNF213 in the host defense against infection. Together, we report that RNF213 assembles into a binding platform for ISGylated proteins on the surface of lipid droplets, acting as a first step of an antimicrobial cellular pathway that processes ISGylated proteins. Our findings provide novel molecular insights into the ISGylation pathway and point towards an important role of the immune response to infection in the etiology of Moyamoya disease. |
HostingRepository | PRIDE |
AnnounceDate | 2021-08-16 |
AnnouncementXML | Submission_2021-08-16_01:18:40.359.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Fabien Thery |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-04-03 00:50:08 | ID requested | |
⏵ 1 | 2021-08-16 01:18:40 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Human, interactome, ISG15 |
Contact List
Francis Impens |
contact affiliation | 1. Center for Medical Biotechnology, VIB, Ghent, Belgium 2. Department for Biomolecular Medicine, Ghent University, Ghent, Belgium 3. VIB Proteomics Core, VIB, Ghent, Belgium |
contact email | francis.impens@vib-ugent.be |
lab head | |
Fabien Thery |
contact affiliation | VIB-UGent |
contact email | fabien.thery91@gmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD018346
- Label: PRIDE project
- Name: Mapping of ISG15 interaction partners by GST pull down coupled to mass spectrometry