Journal article
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
Nature communications, Vol.12(1), pp.5772-5772
10/01/2021
DOI: 10.1038/s41467-021-26061-w
PMCID: PMC8486878
PMID: 34599178
Abstract
ISG15 is an interferon-stimulated, ubiquitin-like protein that can conjugate to substrate proteins (ISGylation) to counteract microbial infection, but the underlying mechanisms remain elusive. Here, we use a virus-like particle trapping technology to identify ISG15-binding proteins and discover Ring Finger Protein 213 (RNF213) as an ISG15 interactor and cellular sensor of ISGylated proteins. RNF213 is a poorly characterized, interferon-induced megaprotein that is frequently mutated in Moyamoya disease, a rare cerebrovascular disorder. We report that interferon induces ISGylation and oligomerization of RNF213 on lipid droplets, where it acts as a sensor for ISGylated proteins. We show that RNF213 has broad antimicrobial activity in vitro and in vivo, counteracting infection with Listeria monocytogenes, herpes simplex virus 1, human respiratory syncytial virus and coxsackievirus B3, and we observe a striking co-localization of RNF213 with intracellular bacteria. Together, our findings provide molecular insights into the ISGylation pathway and reveal RNF213 as a key antimicrobial effector.
Details
- Title: Subtitle
- Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
- Creators
- Fabien Thery - VIB-UGent Center for Medical BiotechnologyLia Martina - VIB-UGent Center for Medical BiotechnologyCaroline Asselman - VIB-UGent Center for Medical BiotechnologyYifeng Zhang - Roy J. and Lucille A. Carver College of MedicineMadeleine Vessely - Roy J. and Lucille A. Carver College of MedicineHeidi Repo - VIB-UGent Center for Medical BiotechnologyKoen Sedeyn - VIB-UGent Center for Medical BiotechnologyGeorge D Moschonas - VIB-UGent Center for Medical BiotechnologyClara Bredow - Humboldt-Universität zu BerlinQi Wen Teo - HKU-Pasteur Research PoleJingshu Zhang - HKU-Pasteur Research PoleKevin Leandro - VIB-UGent Center for Medical BiotechnologyDenzel Eggermont - VIB-UGent Center for Medical BiotechnologyDelphine De Sutter - VIB-UGent Center for Medical BiotechnologyKatie Boucher - VIB-UGent Center for Medical BiotechnologyTino Hochepied - Ghent University HospitalNele Festjens - VIB-UGent Center for Medical BiotechnologyNico Callewaert - VIB-UGent Center for Medical BiotechnologyXavier Saelens - VIB-UGent Center for Medical BiotechnologyBart Dermaut - Ghent University HospitalKlaus-Peter Knobeloch - University of FreiburgAntje Beling - Humboldt-Universität zu BerlinSumana Sanyal - HKU-Pasteur Research PoleLilliana Radoshevich - Roy J. and Lucille A. Carver College of MedicineSven Eyckerman - VIB-UGent Center for Medical BiotechnologyFrancis Impens - VIB-UGent Center for Medical Biotechnology
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.12(1), pp.5772-5772
- DOI
- 10.1038/s41467-021-26061-w
- PMID
- 34599178
- PMCID
- PMC8486878
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Grant note
- Wellcome Trust 220776/Z/20/Z / Wellcome Trust R35 GM137961 / NIGMS NIH HHS MC_PC_19063 / Medical Research Council
- Language
- English
- Date published
- 10/01/2021
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology
- Record Identifier
- 9984297316702771
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