FIP200 Claw Domain Binding to p62 Promotes Autophagosome Formation at Ubiquitin Condensates.
Autophagosomes
/ chemistry
Autophagy
/ genetics
Autophagy-Related Proteins
Crystallography, X-Ray
Humans
Microtubule-Associated Proteins
/ chemistry
Protein Conformation
Protein Interaction Maps
/ genetics
Protein-Tyrosine Kinases
/ chemistry
Proteolysis
Sequestosome-1 Protein
/ chemistry
Signal Transduction
/ genetics
Ubiquitin
/ chemistry
ATG8
X-ray crystallography
biochemistry
cell biology
phase separation
quality control
selective autophagy
ubiquitin
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
18 04 2019
18 04 2019
Historique:
received:
30
05
2018
revised:
13
11
2018
accepted:
24
01
2019
pubmed:
12
3
2019
medline:
19
10
2019
entrez:
12
3
2019
Statut:
ppublish
Résumé
The autophagy cargo receptor p62 facilitates the condensation of misfolded, ubiquitin-positive proteins and their degradation by autophagy, but the molecular mechanism of p62 signaling to the core autophagy machinery is unclear. Here, we show that disordered residues 326-380 of p62 directly interact with the C-terminal region (CTR) of FIP200. Crystal structure determination shows that the FIP200 CTR contains a dimeric globular domain that we designated the "Claw" for its shape. The interaction of p62 with FIP200 is mediated by a positively charged pocket in the Claw, enhanced by p62 phosphorylation, mutually exclusive with the binding of p62 to LC3B, and it promotes degradation of ubiquitinated cargo by autophagy. Furthermore, the recruitment of the FIP200 CTR slows the phase separation of ubiquitinated proteins by p62 in a reconstituted system. Our data provide the molecular basis for a crosstalk between cargo condensation and autophagosome formation.
Identifiants
pubmed: 30853400
pii: S1097-2765(19)30055-3
doi: 10.1016/j.molcel.2019.01.035
pmc: PMC6477179
pii:
doi:
Substances chimiques
Autophagy-Related Proteins
0
MAP1LC3B protein, human
0
Microtubule-Associated Proteins
0
RB1CC1 protein, human
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
Ubiquitin
0
Protein-Tyrosine Kinases
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
330-346.e11Subventions
Organisme : Austrian Science Fund FWF
ID : P 30401
Pays : Austria
Organisme : NIGMS NIH HHS
ID : P30 GM124169
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM111730
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM124149
Pays : United States
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
Références
Annu Rev Biochem. 2017 Jun 20;86:225-244
pubmed: 28301741
BMC Bioinformatics. 2009 Jan 24;10:32
pubmed: 19166624
EMBO Rep. 2014 Aug;15(8):862-70
pubmed: 24968893
Nature. 2015 Jun 18;522(7556):359-62
pubmed: 26040717
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):133-44
pubmed: 20124693
Nat Protoc. 2007;2(8):1896-906
pubmed: 17703201
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Bioinformatics. 2010 Apr 1;26(7):966-8
pubmed: 20147306
J Biol Chem. 2008 Aug 15;283(33):22847-57
pubmed: 18524774
Nature. 2015 Aug 20;524(7565):309-314
pubmed: 26266977
Mol Cell. 2016 Oct 20;64(2):221-235
pubmed: 27768871
Dev Cell. 2002 Dec;3(6):825-37
pubmed: 12479808
Cell Res. 2018 Apr;28(4):405-415
pubmed: 29507397
EMBO Rep. 2013 Mar 1;14(3):284-91
pubmed: 23392225
J Cell Biol. 2001 Apr 16;153(2):381-96
pubmed: 11309418
Methods Enzymol. 1997;276:523-30
pubmed: 9048379
Nat Cell Biol. 2014 Jun;16(6):495-501
pubmed: 24875736
J Biol Chem. 2016 Sep 2;291(36):18799-808
pubmed: 27402840
Nat Cell Biol. 2015 Mar;17(3):262-75
pubmed: 25686248
Acta Neuropathol Commun. 2014 May 03;2:50
pubmed: 24886973
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):479-85
pubmed: 20383001
Mol Cell. 2011 Oct 21;44(2):279-89
pubmed: 22017874
Bioessays. 2010 Feb;32(2):109-18
pubmed: 20091748
FEBS Lett. 2014 Nov 3;588(21):3862-9
pubmed: 25281559
Nature. 1993 Jul 8;364(6433):164-8
pubmed: 8321288
J Biol Chem. 2003 Sep 5;278(36):34568-81
pubmed: 12813044
J Cell Biol. 2011 Jan 10;192(1):17-27
pubmed: 21220506
PLoS Comput Biol. 2017 Oct 24;13(10):e1005817
pubmed: 29065154
Mol Cell. 2010 Apr 23;38(2):265-79
pubmed: 20417604
Mol Cell. 2015 Aug 6;59(3):372-81
pubmed: 26166702
Nat Protoc. 2008;3(7):1171-9
pubmed: 18600222
Hum Mol Genet. 2015 Aug 1;24(15):4429-42
pubmed: 25972374
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
J Biol Chem. 2007 Aug 17;282(33):24131-45
pubmed: 17580304
J Cell Biol. 2014 Oct 13;207(1):91-105
pubmed: 25287303
Nat Struct Mol Biol. 2013 Feb;20(2):144-9
pubmed: 23262492
J Cell Biol. 2005 Nov 21;171(4):603-14
pubmed: 16286508
Elife. 2016 Nov 23;5:
pubmed: 27879200
Nat Protoc. 2016 Dec;11(12):2301-2319
pubmed: 27809316
J Cell Biol. 2008 May 5;181(3):497-510
pubmed: 18443221
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):213-21
pubmed: 20124702
Dev Cell. 2018 Jan 22;44(2):217-232.e11
pubmed: 29290589
J Cell Biol. 2017 May 1;216(5):1301-1320
pubmed: 28404643
J Cell Sci. 2018 Nov 5;131(21):
pubmed: 30397181
Autophagy. 2010 Apr;6(3):330-44
pubmed: 20168092
Mol Cell Biol. 2004 Sep;24(18):8055-68
pubmed: 15340068
EMBO J. 2018 Mar 1;37(5):
pubmed: 29343546
J Mol Biol. 2016 May 8;428(9 Pt A):1714-24
pubmed: 26876603
Genetics. 1989 May;122(1):19-27
pubmed: 2659436
Cell Rep. 2015 May 5;11(5):748-58
pubmed: 25921531
Elife. 2015 Sep 28;4:e08941
pubmed: 26413874
Nature. 2015 Jun 18;522(7556):354-8
pubmed: 26040720
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Nat Cell Biol. 2014 May;16(5):425-433
pubmed: 24705553