Order from disorder in the sarcomere: FATZ forms a fuzzy but tight complex and phase-separated condensates with α-actinin.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
05 2021
Historique:
received: 02 02 2021
accepted: 13 04 2021
entrez: 29 5 2021
pubmed: 30 5 2021
medline: 30 5 2021
Statut: epublish

Résumé

In sarcomeres, α-actinin cross-links actin filaments and anchors them to the Z-disk. FATZ (filamin-, α-actinin-, and telethonin-binding protein of the Z-disk) proteins interact with α-actinin and other core Z-disk proteins, contributing to myofibril assembly and maintenance. Here, we report the first structure and its cellular validation of α-actinin-2 in complex with a Z-disk partner, FATZ-1, which is best described as a conformational ensemble. We show that FATZ-1 forms a tight fuzzy complex with α-actinin-2 and propose an interaction mechanism via main molecular recognition elements and secondary binding sites. The obtained integrative model reveals a polar architecture of the complex which, in combination with FATZ-1 multivalent scaffold function, might organize interaction partners and stabilize α-actinin-2 preferential orientation in Z-disk. Last, we uncover FATZ-1 ability to phase-separate and form biomolecular condensates with α-actinin-2, raising the question whether FATZ proteins can create an interaction hub for Z-disk proteins through membraneless compartmentalization during myofibrillogenesis.

Identifiants

pubmed: 34049882
pii: 7/22/eabg7653
doi: 10.1126/sciadv.abg7653
pmc: PMC8163081
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 201543/Z/16/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : CH/08/001/25300
Pays : United Kingdom
Organisme : Austrian Science Fund FWF
ID : W 1224
Pays : Austria

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Références

Cell Motil Cytoskeleton. 2005 May;61(1):34-48
pubmed: 15810059
Nat Med. 2004 Dec;10(12):1336-43
pubmed: 15543153
Biopolymers. 2008 May;89(5):392-400
pubmed: 17896349
FEBS Lett. 2015 Sep 14;589(19 Pt A):2533-42
pubmed: 26226339
Cell Motil Cytoskeleton. 2008 May;65(5):353-67
pubmed: 18330906
Nature. 2012 Mar 07;483(7389):336-40
pubmed: 22398450
Biophys J. 2011 May 4;100(9):2243-52
pubmed: 21539793
Nucleic Acids Res. 1988 Nov 25;16(22):10881-90
pubmed: 2849754
Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9493-8
pubmed: 9256510
Circ Cardiovasc Genet. 2016 Oct;9(5):426-435
pubmed: 27625337
Nat Protoc. 2013 Sep;8(9):1800-7
pubmed: 23989674
J Muscle Res Cell Motil. 2009;30(5-6):171-85
pubmed: 19830582
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15534-15539
pubmed: 31320587
PLoS Comput Biol. 2009 May;5(5):e1000389
pubmed: 19436721
Prog Mol Biol Transl Sci. 2019;166:1-17
pubmed: 31521229
Science. 2018 Feb 9;359(6376):698-701
pubmed: 29439243
Bioinformatics. 2015 Apr 15;31(8):1325-7
pubmed: 25505092
Nat Biotechnol. 2012 Oct;30(10):918-20
pubmed: 23051804
Nucleic Acids Res. 2018 Jul 2;46(W1):W329-W337
pubmed: 29860432
Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22101-22112
pubmed: 32848067
J Appl Crystallogr. 2015 Mar 12;48(Pt 2):431-443
pubmed: 25844078
Mol Biosyst. 2012 Jan;8(1):268-81
pubmed: 21909575
J Mol Biol. 2018 Aug 3;430(16):2493-2507
pubmed: 29197511
Elife. 2018 Feb 09;7:
pubmed: 29424691
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Protein Sci. 2009 Jul;18(7):1401-24
pubmed: 19544584
J Biol Chem. 2000 Dec 29;275(52):41234-42
pubmed: 10984498
J Appl Crystallogr. 2017 Jun 26;50(Pt 4):1212-1225
pubmed: 28808438
J Mol Biol. 2018 Nov 2;430(23):4603-4606
pubmed: 30213727
Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14632-7
pubmed: 11114196
J Magn Reson. 2007 Oct;188(2):344-56
pubmed: 17822933
Biophys J. 2011 Aug 17;101(4):892-8
pubmed: 21843480
J Biomol NMR. 2010 May;47(1):65-77
pubmed: 20372976
J Magn Reson. 2010 Aug;205(2):286-92
pubmed: 20547466
PLoS Biol. 2021 Apr 12;19(4):e3001148
pubmed: 33844684
Cell. 2016 Jan 28;164(3):487-98
pubmed: 26777405
Bioinformatics. 2014 Sep 1;30(17):2501-2
pubmed: 24825614
Proteins. 2006 Nov 1;65(2):266-73
pubmed: 16948159
Nat Rev Mol Cell Biol. 2017 May;18(5):285-298
pubmed: 28225081
J Biomol NMR. 2016 Aug;65(3-4):193-203
pubmed: 27430223
Curr Opin Struct Biol. 2019 Oct;58:88-96
pubmed: 31252218
J Mol Biol. 2004 Mar 26;337(3):635-45
pubmed: 15019783
Phys Rev A Gen Phys. 1985 Mar;31(3):1695-1697
pubmed: 9895674
J Biol Chem. 2002 Apr 19;277(16):13998-4004
pubmed: 11842093
Bioinformatics. 2017 Jun 15;33(12):1889-1891
pubmed: 28186245
Circulation. 2007 Nov 27;116(22):2587-96
pubmed: 18025526
Handb Exp Pharmacol. 2017;235:39-75
pubmed: 27832381
J Synchrotron Radiat. 2013 Jul;20(Pt 4):660-4
pubmed: 23765312
J Am Chem Soc. 2007 May 2;129(17):5656-64
pubmed: 17411046
Biochemistry. 2018 May 1;57(17):2499-2508
pubmed: 29509422
J Mol Biol. 2018 Nov 2;430(23):4650-4665
pubmed: 29913160
Nucleic Acids Res. 2018 Jan 4;46(D1):D493-D496
pubmed: 29040681
J Cell Sci. 2005 Aug 15;118(Pt 16):3739-49
pubmed: 16076904
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):133-44
pubmed: 20124693
Bioinformatics. 2008 Jun 1;24(11):1344-8
pubmed: 18426805
Cell Mol Life Sci. 2008 Sep;65(17):2688-701
pubmed: 18488141
J Biomol NMR. 2006 Nov;36(3):157-68
pubmed: 17031529
Biotechnol Bioeng. 1990 Feb 20;35(4):327-38
pubmed: 18592527
Structure. 2001 Jul 3;9(7):597-604
pubmed: 11470434
Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W147-51
pubmed: 16844979
Cell. 2014 Dec 4;159(6):1447-60
pubmed: 25433700
J Biomol NMR. 1995 Nov;6(3):277-93
pubmed: 8520220
Science. 2017 Sep 22;357(6357):
pubmed: 28935776
Nat Rev Drug Discov. 2015 May;14(5):313-28
pubmed: 25881969
J Biochem. 1967 Nov;62(5):630-2
pubmed: 4870966
IUCrJ. 2015 Feb 26;2(Pt 2):207-17
pubmed: 25866658
Mol Cell. 2015 Oct 15;60(2):208-19
pubmed: 26412307
Biochim Biophys Acta. 1970 Feb 17;200(2):296-318
pubmed: 4244495
J Mol Biol. 2007 Sep 21;372(3):774-97
pubmed: 17681537
Commun Biol. 2020 Oct 16;3(1):585
pubmed: 33067529
J Clin Invest. 2013 Oct;123(10):4255-63
pubmed: 24091322
Cell Mol Life Sci. 2009 Nov;66(22):3625-39
pubmed: 19690801
EMBO J. 1998 Mar 16;17(6):1614-24
pubmed: 9501083
Bioinformatics. 2005 Jun 15;21(12):2832-8
pubmed: 15802286
Biophys J. 2017 Aug 8;113(3):550-557
pubmed: 28793210
Int J Mol Sci. 2020 Aug 17;21(16):
pubmed: 32824618
FEBS Lett. 2012 Jan 2;586(1):70-3
pubmed: 22138473
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
Nucleic Acids Res. 2015 Jul 1;43(W1):W389-94
pubmed: 25883141
J Biomol NMR. 2012 Sep;54(1):81-95
pubmed: 22806130
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W264-70
pubmed: 24728994
Nat Struct Biol. 2001 Oct;8(10):853-7
pubmed: 11573089
J Exp Biol. 2016 Jan;219(Pt 2):135-45
pubmed: 26792323
Circ Res. 2007 Mar 30;100(6):766-8
pubmed: 17347475
Nat Mater. 2015 Nov;14(11):1164-71
pubmed: 26390327
Nature. 2006 Jan 12;439(7073):229-33
pubmed: 16407954
Acta Crystallogr D Biol Crystallogr. 2012 Apr;68(Pt 4):368-80
pubmed: 22505257
Med Sci Monit. 2008 Jul;14(7):CR372-4
pubmed: 18591919
Trends Cell Biol. 2018 Jun;28(6):420-435
pubmed: 29602697
J Phys Chem B. 2015 Apr 23;119(16):5113-23
pubmed: 25764013
Acta Crystallogr D Struct Biol. 2019 Oct 1;75(Pt 10):861-877
pubmed: 31588918
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1595-600
pubmed: 11171996
J Mol Biol. 2018 Nov 2;430(23):4806-4820
pubmed: 29944854
Amino Acids. 2014 Jun;46(6):1565-82
pubmed: 24647677
Cardiovasc Res. 2013 Jan 1;97(1):44-54
pubmed: 22987565
J Magn Reson. 2009 Apr;197(2):219-28
pubmed: 19185522
Acta Crystallogr D Biol Crystallogr. 2010 Feb;66(Pt 2):125-32
pubmed: 20124692
Biopolymers. 1983 Dec;22(12):2577-637
pubmed: 6667333
Front Cell Dev Biol. 2020 Apr 22;8:267
pubmed: 32391357
J Clin Invest. 2014 Mar;124(3):1144-57
pubmed: 24487589
Biophys Chem. 2001 Nov 28;93(2-3):215-30
pubmed: 11804727
Biochemistry. 2005 Sep 20;44(37):12454-70
pubmed: 16156658
Nucleic Acids Res. 2020 Jan 8;48(D1):D296-D306
pubmed: 31680160
Curr Protein Pept Sci. 2012 Feb;13(1):55-75
pubmed: 22044150
Biochemistry. 1989 Jun 27;28(13):5439-49
pubmed: 2775715
Adv Exp Med Biol. 2008;642:1-14
pubmed: 19181089
Mol Genet Metab. 2007 Apr;90(4):435-40
pubmed: 17254821
J Mol Biol. 2011 Oct 28;413(3):712-25
pubmed: 21925511
Nat Protoc. 2014 Jan;9(1):120-37
pubmed: 24356771
J Clin Invest. 2008 Nov;118(11):3598-608
pubmed: 18846255
J Mol Biol. 1997 Apr 25;268(1):158-69
pubmed: 9149149
J Chem Inf Model. 2011 Oct 24;51(10):2778-86
pubmed: 21919503
Cell Mol Life Sci. 1997 Aug;53(8):621-45
pubmed: 9351466
Protein Sci. 2020 Jan;29(1):66-75
pubmed: 31576635
Bioinformatics. 2018 Jun 1;34(11):1944-1946
pubmed: 29300836
Trends Biochem Sci. 2008 Jan;33(1):2-8
pubmed: 18054235
Cell Rep. 2016 Jun 28;16(1):222-231
pubmed: 27320918
J Biol Chem. 2008 Jul 25;283(30):20959-67
pubmed: 18519573
Bioinformatics. 2016 Feb 15;32(4):616-8
pubmed: 26504146
Mol Cell Biol. 2009 Feb;29(3):822-34
pubmed: 19047374
Nucleic Acids Res. 2007 Jul;35(Web Server issue):W473-6
pubmed: 17584791
J Mol Med (Berl). 2006 Jun;84(6):446-68
pubmed: 16416311
Intrinsically Disord Proteins. 2013 Apr 1;1(1):e24428
pubmed: 28516009
Structure. 2004 Apr;12(4):611-22
pubmed: 15062084
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13392-7
pubmed: 23901099
Anal Biochem. 2000 Dec 15;287(2):252-60
pubmed: 11112271
Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2131-2136
pubmed: 28202730
J Appl Crystallogr. 2007 Aug 1;40(Pt 4):658-674
pubmed: 19461840
Nat Plants. 2020 Dec;6(12):1480-1490
pubmed: 33230314
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Mol Cell Proteomics. 2015 Apr;14(4):1137-47
pubmed: 25648531
Mol Genet Metab. 2007 Jun;91(2):207-8
pubmed: 17434779
Biophys J. 2017 May 23;112(10):2038-2042
pubmed: 28487147
J Biomol NMR. 1994 Mar;4(2):301-6
pubmed: 8019138
Mol Microbiol. 2013 Nov;90(4):744-55
pubmed: 24033548
J Biomol NMR. 2012 Apr;52(4):329-37
pubmed: 22350953
Nucleic Acids Res. 2018 Jan 4;46(D1):D471-D476
pubmed: 29136219
J Appl Crystallogr. 2012 Mar 15;45(Pt 2):342-350
pubmed: 25484842
Mol Cell. 2017 May 18;66(4):447-457.e7
pubmed: 28506462
Protein Sci. 2002 Apr;11(4):739-56
pubmed: 11910019
Proteins. 2010 Jun;78(8):1950-8
pubmed: 20408171
Nucleic Acids Res. 2014 Jul;42(Web Server issue):W320-4
pubmed: 24753421
J Magn Reson. 2007 Feb;184(2):185-95
pubmed: 17084097

Auteurs

Antonio Sponga (A)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Joan L Arolas (JL)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Thomas C Schwarz (TC)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Cy M Jeffries (CM)

European Molecular Biology Laboratory (EMBL), Hamburg Unit, Hamburg, Germany.

Ariadna Rodriguez Chamorro (A)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Julius Kostan (J)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Andrea Ghisleni (A)

King's College London BHF Centre for Research Excellence, Randall Centre for Cell and Molecular Biophysics, London SE1 1UL, UK.

Friedel Drepper (F)

Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany.

Anton Polyansky (A)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.
National Research University Higher School of Economics, Moscow 101000, Russia.

Euripedes De Almeida Ribeiro (E)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Miriam Pedron (M)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Anna Zawadzka-Kazimierczuk (A)

Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland.

Georg Mlynek (G)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Thomas Peterbauer (T)

Department of Biochemistry and Cell Biology, Max Perutz Labs, University of Vienna, Dr. BohrGasse 9, A-1030 Vienna, Austria.

Pierantonio Doto (P)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Claudia Schreiner (C)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Eneda Hollerl (E)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Borja Mateos (B)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Leonhard Geist (L)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Georgine Faulkner (G)

Department of Biology, University of Padova, 35100 Padova, Italy.

Wiktor Kozminski (W)

Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland.

Dmitri I Svergun (DI)

King's College London BHF Centre for Research Excellence, Randall Centre for Cell and Molecular Biophysics, London SE1 1UL, UK.

Bettina Warscheid (B)

Biochemistry and Functional Proteomics, Institute of Biology II, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Signalling Research Centres BIOSS and CIBSS, University of Freiburg, 79104 Freiburg, Germany.

Bojan Zagrovic (B)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Mathias Gautel (M)

King's College London BHF Centre for Research Excellence, Randall Centre for Cell and Molecular Biophysics, London SE1 1UL, UK.

Robert Konrat (R)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria.

Kristina Djinović-Carugo (K)

Department of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Campus Vienna Biocenter 5, A-1030 Vienna, Austria. kristina.djinovic@univie.ac.at.
Department of Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.

Classifications MeSH