Ring finger protein 213 assembles into a sensor for ISGylated proteins with antimicrobial activity.
A549 Cells
Adenosine Triphosphatases
/ metabolism
Animals
Anti-Infective Agents
/ metabolism
Cytokines
/ metabolism
Enterovirus
/ physiology
HEK293 Cells
HeLa Cells
Herpesvirus 1, Human
/ physiology
Humans
Interferon Type I
/ metabolism
Lipid Droplets
/ metabolism
Listeria monocytogenes
/ physiology
Male
Mice, Inbred C57BL
Protein Binding
Protein Multimerization
Small Ubiquitin-Related Modifier Proteins
/ metabolism
THP-1 Cells
Ubiquitin
/ metabolism
Ubiquitin-Protein Ligases
/ metabolism
Ubiquitins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
10
03
2021
accepted:
14
09
2021
entrez:
2
10
2021
pubmed:
3
10
2021
medline:
19
3
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34599178
doi: 10.1038/s41467-021-26061-w
pii: 10.1038/s41467-021-26061-w
pmc: PMC8486878
doi:
Substances chimiques
Anti-Infective Agents
0
Cytokines
0
Interferon Type I
0
Small Ubiquitin-Related Modifier Proteins
0
Ubiquitin
0
Ubiquitins
0
ISG15 protein, human
60267-61-0
RNF213 protein, human
EC 2.3.2.27
Ubiquitin-Protein Ligases
EC 2.3.2.27
Adenosine Triphosphatases
EC 3.6.1.-
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5772Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19063
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : R35 GM137961
Pays : United States
Organisme : Wellcome Trust
ID : 220776/Z/20/Z
Pays : United Kingdom
Informations de copyright
© 2021. The Author(s).
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