Structures of autoinhibited and polymerized forms of CARD9 reveal mechanisms of CARD9 and CARD11 activation.
B-Cell CLL-Lymphoma 10 Protein
/ metabolism
CARD Signaling Adaptor Proteins
/ genetics
Cryoelectron Microscopy
Guanylate Cyclase
/ genetics
HEK293 Cells
Humans
Mutation
Nuclear Magnetic Resonance, Biomolecular
Protein Conformation, alpha-Helical
Protein Domains
Protein Multimerization
/ immunology
Recombinant Proteins
/ genetics
Signal Transduction
/ immunology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 07 2019
11 07 2019
Historique:
received:
15
01
2019
accepted:
06
06
2019
entrez:
13
7
2019
pubmed:
13
7
2019
medline:
28
10
2019
Statut:
epublish
Résumé
CARD9 and CARD11 drive immune cell activation by nucleating Bcl10 polymerization, but are held in an autoinhibited state prior to stimulation. Here, we elucidate the structural basis for this autoinhibition by determining the structure of a region of CARD9 that includes an extensive interface between its caspase recruitment domain (CARD) and coiled-coil domain. We demonstrate, for both CARD9 and CARD11, that disruption of this interface leads to hyperactivation in cells and to the formation of Bcl10-templating filaments in vitro, illuminating the mechanism of action of numerous oncogenic mutations of CARD11. These structural insights enable us to characterize two similar, yet distinct, mechanisms by which autoinhibition is relieved in the course of canonical CARD9 or CARD11 activation. We also dissect the molecular determinants of helical template assembly by solving the structure of the CARD9 filament. Taken together, these findings delineate the structural mechanisms of inhibition and activation within this protein family.
Identifiants
pubmed: 31296852
doi: 10.1038/s41467-019-10953-z
pii: 10.1038/s41467-019-10953-z
pmc: PMC6624267
doi:
Substances chimiques
B-Cell CLL-Lymphoma 10 Protein
0
BCL10 protein, human
0
CARD Signaling Adaptor Proteins
0
CARD9 protein, human
0
Recombinant Proteins
0
CARD11 protein, human
EC 4.6.1.2
Guanylate Cyclase
EC 4.6.1.2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3070Références
Nature. 2012 Mar 07;483(7389):336-40
pubmed: 22398450
J Mol Biol. 1997 Oct 17;273(1):283-98
pubmed: 9367762
J Struct Biol. 2007 Jan;157(1):117-25
pubmed: 16828314
Nat Immunol. 2007 Jan;8(1):31-8
pubmed: 17159984
N Engl J Med. 2013 Oct 31;369(18):1704-1714
pubmed: 24131138
Nat Struct Mol Biol. 2016 May;23(5):416-25
pubmed: 27043298
J Biol Chem. 2016 Apr 15;291(16):8338-48
pubmed: 26884334
Nature. 2009 Jun 4;459(7247):717-21
pubmed: 19412164
Mol Cell. 2010 Jun 11;38(5):627-35
pubmed: 20541996
FEBS Lett. 2001 May 11;496(2-3):121-7
pubmed: 11356195
J Struct Biol. 2013 Nov;184(2):226-36
pubmed: 23954653
Curr Opin Hematol. 2016 Jul;23(4):402-9
pubmed: 27135977
Proteins. 2005 Jun 1;59(4):687-96
pubmed: 15815974
Nat Rev Immunol. 2004 May;4(5):348-59
pubmed: 15122200
Science. 1991 May 24;252(5009):1162-4
pubmed: 2031185
Nat Protoc. 2007;2(11):2728-33
pubmed: 18007608
J Exp Med. 2012 Nov 19;209(12):2247-61
pubmed: 23129749
Nat Methods. 2009 Jul;6(7):500-2
pubmed: 19483691
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18898-903
pubmed: 24191053
Nature. 2010 Oct 14;467(7317):805-10
pubmed: 20944740
Curr Biol. 2003 Jul 15;13(14):1252-8
pubmed: 12867038
Nat Commun. 2018 Oct 2;9(1):4043
pubmed: 30279485
J Struct Biol. 2007 Jan;157(1):38-46
pubmed: 16859925
Trends Immunol. 2009 May;30(5):234-42
pubmed: 19359218
Mol Syst Biol. 2011 Oct 11;7:539
pubmed: 21988835
Front Immunol. 2018 Sep 19;9:2105
pubmed: 30283447
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Elife. 2018 Mar 07;7:
pubmed: 29513216
J Biol Chem. 2018 Oct 26;293(43):16803-16817
pubmed: 30206119
J Biomol NMR. 2009 Aug;44(4):213-23
pubmed: 19548092
J Allergy Clin Immunol. 2014 Aug;134(2):276-84
pubmed: 25087226
Nat Genet. 2011 Oct 09;43(11):1066-73
pubmed: 21983784
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
pubmed: 9757107
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3023-8
pubmed: 18287044
Immunity. 2015 Oct 20;43(4):715-26
pubmed: 26488816
Anal Chem. 2017 Jan 17;89(2):1049-1053
pubmed: 28024318
Mol Cell Biol. 2008 Sep;28(18):5668-86
pubmed: 18625728
J Biol Chem. 2016 Apr 15;291(16):8324-36
pubmed: 26884335
Annu Rev Biochem. 2008;77:363-82
pubmed: 18410248
J Struct Biol. 2017 Jun;198(3):163-176
pubmed: 28193500
Curr Opin Struct Biol. 2012 Apr;22(2):241-7
pubmed: 22429337
Immunity. 2005 Dec;23(6):561-74
pubmed: 16356855
Mol Cell Biol. 2013 Jan;33(2):429-43
pubmed: 23149938
J Struct Biol. 2014 Jan;185(1):15-26
pubmed: 24269218
Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10845-10852
pubmed: 30279182
J Biol Chem. 2016 Dec 9;291(50):25921-25936
pubmed: 27777308
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Mol Cell. 2018 Jul 5;71(1):155-168.e7
pubmed: 29979963
J Exp Med. 2007 Dec 24;204(13):3285-93
pubmed: 18086859
Biochemistry. 2010 Sep 28;49(38):8240-50
pubmed: 20799731
Science. 2008 Mar 21;319(5870):1676-9
pubmed: 18323416
J Am Soc Mass Spectrom. 2012 Dec;23(12):2132-9
pubmed: 22965280
N Engl J Med. 2009 Oct 29;361(18):1727-35
pubmed: 19864672
Proc Natl Acad Sci U S A. 2018 Feb 13;115(7):1499-1504
pubmed: 29382759
Nat Genet. 2015 Nov;47(11):1304-15
pubmed: 26437031
Immunity. 2010 May 28;32(5):681-91
pubmed: 20493731
J Am Soc Mass Spectrom. 2011 Nov;22(11):1906-15
pubmed: 21952778
Mol Cell. 2014 Aug 21;55(4):511-23
pubmed: 25018021
Front Immunol. 2018 Aug 06;9:1836
pubmed: 30127791
Mol Cell. 2013 Sep 26;51(6):766-79
pubmed: 24074955
J Allergy Clin Immunol. 2015 Jun;135(6):1558-68.e2
pubmed: 25702837
Immunity. 2012 Jan 27;36(1):32-42
pubmed: 22265677
J Exp Med. 2009 Aug 31;206(9):2037-51
pubmed: 19703985
J Am Soc Mass Spectrom. 2011 Nov;22(11):1898-905
pubmed: 21952777
J Mol Biol. 2002 May 24;319(1):209-27
pubmed: 12051947
Protein Expr Purif. 2005 May;41(1):207-34
pubmed: 15915565
J Immunol. 2008 Jun 1;180(11):7404-13
pubmed: 18490740
JCI Insight. 2016 Oct 20;1(17):e89890
pubmed: 27777981
J Struct Biol. 2012 Dec;180(3):519-30
pubmed: 23000701