The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 11 2023
11 11 2023
Historique:
received:
27
03
2023
accepted:
25
10
2023
medline:
13
11
2023
pubmed:
12
11
2023
entrez:
11
11
2023
Statut:
epublish
Résumé
RIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of which is ubiquitination of the RIG-I Caspase Recruitment Domains (CARDs) by E3 ligase Riplet. This is required for interaction between RIG-I and its downstream adapter protein MAVS, but the mechanism of action remains unclear. Here we show that Riplet is required for RIG-I signaling in the presence of both short and long dsRNAs, establishing that Riplet activation does not depend upon RIG-I filament formation on long dsRNAs. Likewise, quantitative Riplet-RIG-I affinity measurements establish that Riplet interacts with RIG-I regardless of whether the receptor is bound to RNA. To understand this, we solved high-resolution cryo-EM structures of RIG-I/RNA/Riplet complexes, revealing molecular interfaces that control Riplet-mediated activation and enabling the formulation of a unified model for the role of Riplet in signaling.
Identifiants
pubmed: 37951994
doi: 10.1038/s41467-023-42982-0
pii: 10.1038/s41467-023-42982-0
pmc: PMC10640585
doi:
Substances chimiques
Ubiquitin-Protein Ligases
EC 2.3.2.27
DEAD Box Protein 58
EC 3.6.4.13
RNA, Double-Stranded
0
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
7308Subventions
Organisme : NIAID NIH HHS
ID : R01 AI131518
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Protein Sci. 2018 Jan;27(1):293-315
pubmed: 29067766
Sci Adv. 2019 Oct 02;5(10):eaax3641
pubmed: 31616790
J Struct Biol. 2015 Nov;192(2):216-21
pubmed: 26278980
Sci Rep. 2016 Jul 08;6:29263
pubmed: 27387525
J Biol Chem. 2009 Jan 9;284(2):807-17
pubmed: 19017631
Nat Commun. 2018 May 8;9(1):1820
pubmed: 29739942
Immunol Rev. 2021 Nov;304(1):154-168
pubmed: 34514601
Cell Rep. 2015 Aug 4;12(5):788-97
pubmed: 26212332
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
EMBO Rep. 2013 Sep;14(9):772-9
pubmed: 23897087
Life Sci Alliance. 2023 Aug 9;6(10):
pubmed: 37558422
Signal Transduct Target Ther. 2021 Aug 4;6(1):291
pubmed: 34344870
Mol Cell. 2021 Feb 4;81(3):599-613.e8
pubmed: 33373584
Nature. 2007 Apr 19;446(7138):916-920
pubmed: 17392790
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Immunol Rev. 2022 Aug;309(1):12-24
pubmed: 35775361
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Mol Cell. 2023 Jan 5;83(1):90-104.e4
pubmed: 36521492
Mol Cell. 2022 Nov 3;82(21):4131-4144.e6
pubmed: 36272408
Nat Methods. 2022 Jun;19(6):679-682
pubmed: 35637307
Curr Opin Microbiol. 2014 Aug;20:76-81
pubmed: 24912143
Immunity. 2012 Jun 29;36(6):959-73
pubmed: 22705106
Acta Crystallogr D Struct Biol. 2017 Jun 1;73(Pt 6):469-477
pubmed: 28580908
EMBO J. 2016 Jun 1;35(11):1204-18
pubmed: 27154206
Cell. 2019 May 16;177(5):1187-1200.e16
pubmed: 31006531
IUCrJ. 2019 Jan 01;6(Pt 1):5-17
pubmed: 30713699
J Mol Biol. 2003 Oct 31;333(4):721-45
pubmed: 14568533
Nature. 2014 May 1;509(7498):110-4
pubmed: 24590070
Elife. 2015 Sep 15;4:
pubmed: 26371557
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
RNA. 2012 Dec;18(12):2118-27
pubmed: 23118418
Elife. 2018 Nov 09;7:
pubmed: 30412051
Acta Crystallogr D Struct Biol. 2018 Sep 1;74(Pt 9):814-840
pubmed: 30198894
Curr Opin Virol. 2022 Feb;52:30-38
pubmed: 34814102
Nucleic Acids Res. 1995 Jul 25;23(14):2677-84
pubmed: 7544462
Annu Rev Med. 2016;67:323-36
pubmed: 26526766
J Virol. 2015 Jun;89(11):6067-79
pubmed: 25810557
Nat Immunol. 2022 Feb;23(2):165-176
pubmed: 35105981
Nat Methods. 2017 Apr;14(4):331-332
pubmed: 28250466
Mol Cell. 2013 Sep 12;51(5):573-83
pubmed: 23993742
Nat Protoc. 2013 Nov;8(11):2281-2308
pubmed: 24157548
PLoS One. 2009 Jun 01;4(6):e5760
pubmed: 19484123
Mol Cell. 2014 Aug 21;55(4):511-23
pubmed: 25018021
Biochem Soc Trans. 2020 Dec 18;48(6):2615-2624
pubmed: 33170204
Nat Commun. 2017 May 04;8:15138
pubmed: 28469175
Cell Host Microbe. 2010 Dec 16;8(6):496-509
pubmed: 21147464
Sci Adv. 2018 Feb 21;4(2):e1701854
pubmed: 29492454
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
STAR Protoc. 2023 Mar 14;4(2):102166
pubmed: 36920909