Journal article
Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, 7.7MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-021-26061-w
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 12
- Issue:
- 1
- Article number:
- 5772
- Publication date:
- 2021-10-01
- Acceptance date:
- 2021-09-14
- DOI:
- EISSN:
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2041-1723
- Pmid:
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34599178
- Language:
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English
- Keywords:
- Pubs id:
-
1198434
- Local pid:
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pubs:1198434
- Deposit date:
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2022-01-04
Terms of use
- Copyright holder:
- Thery et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s) 2021. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- Licence:
- CC Attribution (CC BY)
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