Programmable de novo designed coiled coil-mediated phase separation in mammalian cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 Dec 2023
02 Dec 2023
Historique:
received:
29
06
2023
accepted:
17
11
2023
medline:
4
12
2023
pubmed:
3
12
2023
entrez:
2
12
2023
Statut:
epublish
Résumé
Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. The design of liquid-liquid phase separated (LLPS) condensates based on de novo designed tunable modules that interact in a well-understood, controllable manner could improve our understanding of this phenomenon and enable the introduction of new features. Here we report the construction of CC-LLPS in mammalian cells, based on designed coiled-coil (CC) dimer-forming modules, where the stability of CC pairs, their number, linkers, and sequential arrangement govern the transition between diffuse, liquid and immobile condensates and are corroborated by coarse-grained molecular simulations. Through modular design, we achieve multiple coexisting condensates, chemical regulation of LLPS, condensate fusion, formation from either one or two polypeptide components or LLPS regulation by a third polypeptide chain. These findings provide further insights into the principles underlying LLPS formation and a design platform for controlling biological processes.
Identifiants
pubmed: 38042897
doi: 10.1038/s41467-023-43742-w
pii: 10.1038/s41467-023-43742-w
pmc: PMC10693550
doi:
Substances chimiques
Peptides
0
Intrinsically Disordered Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7973Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM065103
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
Mol Cell. 2015 Mar 5;57(5):936-947
pubmed: 25747659
J Biol Chem. 2021 Sep;297(3):100998
pubmed: 34302807
Biophys J. 1998 Jul;75(1):422-7
pubmed: 9649402
Cell. 2016 Jul 28;166(3):651-663
pubmed: 27374333
Elife. 2017 Nov 01;6:
pubmed: 29091028
Nat Commun. 2021 Dec 9;12(1):7157
pubmed: 34887424
J Biochem. 2021 Oct 11;170(2):153-162
pubmed: 34358306
Nat Methods. 2009 May;6(5):343-5
pubmed: 19363495
Neuron. 2017 Mar 8;93(5):995-1002
pubmed: 28279363
Nature. 2012 Mar 07;483(7389):336-40
pubmed: 22398450
Curr Opin Struct Biol. 2016 Dec;41:180-186
pubmed: 27552079
Dev Cell. 2020 Oct 12;55(1):30-44
pubmed: 32726575
Nat Chem. 2023 Sep 14;:
pubmed: 37710047
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7189-94
pubmed: 26015579
FEBS Lett. 2020 Oct;594(19):3086-3094
pubmed: 32668013
Cell. 2018 Nov 29;175(6):1467-1480.e13
pubmed: 30500534
Nat Chem Biol. 2019 Feb;15(2):115-122
pubmed: 30531965
Nat Struct Mol Biol. 2019 Jul;26(7):637-648
pubmed: 31270472
J Phys Chem Lett. 2019 Jul 18;10(14):3929-3936
pubmed: 31260322
JACS Au. 2022 Jun 13;2(7):1506-1521
pubmed: 35911447
Annu Rev Biophys. 2019 May 6;48:465-494
pubmed: 30951647
Biochemistry. 2018 May 1;57(17):2424-2431
pubmed: 29381060
Front Cell Dev Biol. 2020 Nov 19;8:607947
pubmed: 33330512
J Mol Biol. 1998 Nov 20;284(1):173-91
pubmed: 9811549
Cell. 2018 Nov 29;175(6):1481-1491.e13
pubmed: 30500535
Science. 2016 Apr 29;352(6285):595-9
pubmed: 27056844
Nat Rev Mol Cell Biol. 2017 May;18(5):285-298
pubmed: 28225081
PLoS Comput Biol. 2019 Oct 21;15(10):e1007028
pubmed: 31634364
Front Neurosci. 2019 Aug 13;13:845
pubmed: 31456657
Nat Commun. 2023 Dec 2;14(1):7973
pubmed: 38042897
Science. 2020 Feb 7;367(6478):694-699
pubmed: 32029630
Curr Opin Cell Biol. 2019 Oct;60:92-98
pubmed: 31176175
Methods. 2015 Apr;76:137-148
pubmed: 25477226
Nat Commun. 2020 Jan 14;11(1):270
pubmed: 31937751
Cell. 2021 Sep 16;184(19):4886-4903.e21
pubmed: 34433013
J Am Chem Soc. 2017 Jun 21;139(24):8229-8236
pubmed: 28553984
Science. 2009 Jun 26;324(5935):1729-32
pubmed: 19460965
DNA Repair (Amst). 2021 Sep;105:103170
pubmed: 34256335
Nat Chem. 2020 Sep;12(9):814-825
pubmed: 32747754
Annu Rev Phys Chem. 2020 Apr 20;71:53-75
pubmed: 32312191
Protein Sci. 2022 May;31(5):e4317
pubmed: 35481633
Nat Chem Biol. 2023 Apr;19(4):518-528
pubmed: 36747054
Cell. 2017 Jan 12;168(1-2):159-171.e14
pubmed: 28041848
Science. 2017 Sep 22;357(6357):
pubmed: 28935776
Nat Chem Biol. 2022 Dec;18(12):1319-1329
pubmed: 36400992
ACS Synth Biol. 2012 Apr 20;1(4):118-29
pubmed: 22558529
Nature. 2019 May;569(7755):265-269
pubmed: 31043738
Cell Syst. 2018 Jun 27;6(6):655-663.e5
pubmed: 29859829
Curr Opin Struct Biol. 2021 Apr;67:41-50
pubmed: 33069007
J Cell Biol. 2021 May 3;220(5):
pubmed: 33704371
Cell. 2019 Jan 24;176(3):419-434
pubmed: 30682370
Adv Protein Chem. 2005;70:79-112
pubmed: 15837514
Mol Cell. 2015 Oct 15;60(2):208-19
pubmed: 26412307
J Cell Sci. 2019 Nov 21;132(22):
pubmed: 31754043
Science. 2020 Mar 13;367(6483):
pubmed: 32165560
Cell. 2015 Sep 24;163(1):123-33
pubmed: 26406374
Mol Cell. 2016 Jul 7;63(1):72-85
pubmed: 27392146
Elife. 2014 Oct 16;3:
pubmed: 25321392
Nucleic Acids Res. 2021 Mar 18;49(5):2931-2945
pubmed: 33577679
J Cell Sci. 2021 Jul 15;134(14):
pubmed: 34308971
J Pept Sci. 2011 Feb;17(2):100-6
pubmed: 21234981
Nat Commun. 2022 Sep 26;13(1):5643
pubmed: 36163138
Nat Rev Mol Cell Biol. 2021 Mar;22(3):196-213
pubmed: 33510441
Nat Chem Biol. 2022 Dec;18(12):1298-1306
pubmed: 35761089
Nat Commun. 2023 Jan 26;14(1):421
pubmed: 36702825
Anal Chem. 2012 Jun 5;84(11):5066-73
pubmed: 22530732
Nat Cell Biol. 2020 Apr;22(4):453-464
pubmed: 32203417
Nat Chem Biol. 2015 Mar;11(3):221-8
pubmed: 25664692
Nat Chem Biol. 2020 Sep;16(9):939-945
pubmed: 32661377
Dev Cell. 2002 Nov;3(5):673-84
pubmed: 12431374
Nat Chem Biol. 2013 Jun;9(6):362-6
pubmed: 23624438
Proc Natl Acad Sci U S A. 2011 Mar 15;108(11):4334-9
pubmed: 21368180
J Cell Biol. 2017 Apr 3;216(4):983-997
pubmed: 28264915
Cell. 2016 Jun 16;165(7):1686-1697
pubmed: 27212236
Mol Cell. 2018 Jan 18;69(2):334-346.e4
pubmed: 29307513
Nat Chem Biol. 2020 May;16(5):513-519
pubmed: 31907374
Annu Rev Biophys. 2020 May 6;49:107-133
pubmed: 32004090
Biochemistry. 2022 Nov 15;61(22):2443-2455
pubmed: 35802394
FASEB J. 2022 Jul;36(7):e22425
pubmed: 35747925
Science. 2019 Mar 29;363(6434):
pubmed: 30923194