Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 09 2023
08 09 2023
Historique:
received:
27
04
2023
accepted:
29
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
Prion-like low-complexity domains (PLCDs) are involved in the formation and regulation of distinct biomolecular condensates that form via phase separation coupled to percolation. Intracellular condensates often encompass numerous distinct proteins with PLCDs. Here, we combine simulations and experiments to study mixtures of PLCDs from two RNA-binding proteins, hnRNPA1 and FUS. Using simulations and experiments, we find that 1:1 mixtures of A1-LCD and FUS-LCD undergo phase separation more readily than either of the PLCDs on their own due to complementary electrostatic interactions. Tie line analysis reveals that stoichiometric ratios of different components and their sequence-encoded interactions contribute jointly to the driving forces for condensate formation. Simulations also show that the spatial organization of PLCDs within condensates is governed by relative strengths of homotypic versus heterotypic interactions. We uncover rules for how interaction strengths and sequence lengths modulate conformational preferences of molecules at interfaces of condensates formed by mixtures of proteins.
Identifiants
pubmed: 37684240
doi: 10.1038/s41467-023-41274-x
pii: 10.1038/s41467-023-41274-x
pmc: PMC10491635
doi:
Substances chimiques
Prions
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
5527Commentaires et corrections
Type : UpdateOf
Type : UpdateOf
Informations de copyright
© 2023. Springer Nature Limited.
Références
Science. 2020 Feb 7;367(6478):694-699
pubmed: 32029630
Cell. 2016 Jul 28;166(3):651-663
pubmed: 27374333
Proc Natl Acad Sci U S A. 2021 Mar 9;118(10):
pubmed: 33653957
Nature. 2020 May;581(7807):209-214
pubmed: 32405004
Nature. 2012 Mar 07;483(7389):336-40
pubmed: 22398450
Cell. 2015 Aug 27;162(5):1066-77
pubmed: 26317470
Nat Chem. 2022 Feb;14(2):196-207
pubmed: 34931046
PLoS Comput Biol. 2018 Jan 24;14(1):e1005941
pubmed: 29364893
Nature. 2019 Aug;572(7770):543-548
pubmed: 31391587
Prion. 2011 Jul-Sep;5(3):179-87
pubmed: 21847013
Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2202222119
pubmed: 35787038
Nat Commun. 2021 Feb 8;12(1):872
pubmed: 33558506
J Chem Phys. 2015 Dec 28;143(24):243123
pubmed: 26723608
Nat Chem Biol. 2022 Jan;18(1):70-80
pubmed: 34916619
Proc Natl Acad Sci U S A. 2015 Jun 9;112(23):7189-94
pubmed: 26015579
Nature. 2022 Sep;609(7926):255-264
pubmed: 36071192
Nat Phys. 2022;18(5):571-578
pubmed: 35582428
Nat Rev Mol Cell Biol. 2021 Mar;22(3):183-195
pubmed: 32632317
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11):
pubmed: 33688043
Nat Comput Sci. 2021 Nov;1(11):732-743
pubmed: 35795820
Science. 2018 Jul 27;361(6400):
pubmed: 29930091
Biomolecules. 2022 Oct 14;12(10):
pubmed: 36291688
Biochemistry. 2021 Nov 30;60(47):3566-3581
pubmed: 34784177
Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2120799119
pubmed: 35333653
Nat Chem. 2023 Oct;15(10):1340-1349
pubmed: 37749234
Curr Opin Struct Biol. 2023 Apr;79:102540
pubmed: 36804705
Traffic. 2019 Sep;20(9):650-660
pubmed: 31218815
Bioinformatics. 2014 Sep 1;30(17):2501-2
pubmed: 24825614
RNA. 2022 Jan;28(1):27-35
pubmed: 34772789
Science. 2018 Aug 10;361(6402):604-607
pubmed: 29976799
Nat Rev Mol Cell Biol. 2017 May;18(5):285-298
pubmed: 28225081
PLoS Comput Biol. 2019 Oct 21;15(10):e1007028
pubmed: 31634364
Elife. 2021 Jun 09;10:
pubmed: 34106046
Dev Cell. 2020 Dec 7;55(5):588-602.e7
pubmed: 33290695
Elife. 2020 Jun 19;9:
pubmed: 32553117
Proc Natl Acad Sci U S A. 2021 Dec 21;118(51):
pubmed: 34916288
Nat Chem. 2017 Nov;9(11):1118-1125
pubmed: 29064502
Proc Natl Acad Sci U S A. 2019 Sep 24;116(39):19474-19483
pubmed: 31506351
Science. 2018 Jul 27;361(6400):412-415
pubmed: 29930094
Science. 2009 Jun 26;324(5935):1729-32
pubmed: 19460965
Nat Chem Biol. 2023 Apr;19(4):518-528
pubmed: 36747054
Proc Natl Acad Sci U S A. 2021 Dec 14;118(50):
pubmed: 34887356
Science. 2017 Sep 22;357(6357):
pubmed: 28935776
Biophys Rev (Melville). 2021 Jun;2(2):021302
pubmed: 34179888
Chem Rev. 2023 Jul 26;123(14):8945-8987
pubmed: 36881934
Biochemistry. 2021 Nov 2;60(43):3213-3222
pubmed: 34648275
Cell Rep. 2018 Jun 12;23(11):3327-3339
pubmed: 29898402
Soft Matter. 2020 Mar 28;16(12):2885-2914
pubmed: 32134099
Cell. 2015 Sep 24;163(1):123-33
pubmed: 26406374
Cell. 2013 Aug 15;154(4):727-36
pubmed: 23953108
Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):5826-5835
pubmed: 32127480
Proc Natl Acad Sci U S A. 2021 Jun 22;118(25):
pubmed: 34135122
Mol Cell. 2016 Jul 7;63(1):72-85
pubmed: 27392146
Science. 2020 Oct 2;370(6512):56-60
pubmed: 33004511
Cell. 2020 Apr 16;181(2):306-324.e28
pubmed: 32302570
Rep Prog Phys. 2018 Apr;81(4):046601
pubmed: 29313527
Science. 2021 Sep 10;373(6560):1218-1224
pubmed: 34516789
Cell. 2018 Jul 26;174(3):688-699.e16
pubmed: 29961577
Mol Cell. 2020 Jul 2;79(1):54-67.e7
pubmed: 32521226
Cell. 2020 Apr 16;181(2):346-361.e17
pubmed: 32302572
Elife. 2017 Nov 01;6:
pubmed: 29091028
Science. 2019 Mar 8;363(6431):1093-1097
pubmed: 30846599
Nat Cell Biol. 2019 Dec;21(12):1578-1589
pubmed: 31792379
Nat Rev Mol Cell Biol. 2021 Mar;22(3):196-213
pubmed: 33510441
Science. 2018 Jan 5;359(6371):
pubmed: 29301985
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):
pubmed: 33547245
Mol Cell. 2021 Mar 4;81(5):1013-1026.e11
pubmed: 33548202
Cell. 2022 Nov 23;185(24):4488-4506.e20
pubmed: 36318922
Nat Rev Mol Cell Biol. 2021 Mar;22(3):215-235
pubmed: 33169001
Curr Opin Struct Biol. 2019 Feb;54:171-178
pubmed: 30978654
Science. 2018 May 25;360(6391):922-927
pubmed: 29650703
Proc Natl Acad Sci U S A. 2020 Jun 16;117(24):13238-13247
pubmed: 32482873
J Cell Biol. 2022 May 2;221(5):
pubmed: 35293953
Cell. 2018 Nov 29;175(6):1492-1506.e19
pubmed: 30449617
Chem Sci. 2023 Jan 25;14(7):1820-1836
pubmed: 36819870
Nature. 2013 Mar 28;495(7442):467-73
pubmed: 23455423
Macromolecules. 2021 Jul 27;54(14):6878-6890
pubmed: 34334816
J Cell Biol. 2022 Dec 5;221(12):
pubmed: 36173346
Proc Natl Acad Sci U S A. 2020 May 26;117(21):11421-11431
pubmed: 32393642
Biochem J. 2020 Sep 30;477(18):3471-3497
pubmed: 32965492
Nat Commun. 2022 Dec 13;13(1):7722
pubmed: 36513655
Nucleic Acids Res. 2020 Jan 8;48(D1):D288-D295
pubmed: 31691822
Mol Cell. 2022 Jun 16;82(12):2201-2214
pubmed: 35675815
Nucleic Acids Res. 2022 Jun 24;50(11):6300-6312
pubmed: 35687109
Phys Rev E. 2020 Oct;102(4-1):042403
pubmed: 33212590
Int J Mol Sci. 2021 Jan 27;22(3):
pubmed: 33513942
Nat Rev Mol Cell Biol. 2023 Apr;24(4):288-304
pubmed: 36424481
J Mol Biol. 2018 Nov 2;430(23):4666-4684
pubmed: 30099028
Biophys J. 2021 Apr 6;120(7):1288-1300
pubmed: 33640380
J Chem Phys. 2018 Oct 28;149(16):163308
pubmed: 30384692
J Cell Biol. 2015 Mar 2;208(5):533-44
pubmed: 25713414
Mol Cell. 2022 Sep 1;82(17):3193-3208.e8
pubmed: 35853451
Biophys J. 2018 Jul 3;115(1):3-8
pubmed: 29972809
Cell. 2016 Jun 16;165(7):1686-1697
pubmed: 27212236
Dev Cell. 2019 Sep 23;50(6):716-728.e6
pubmed: 31402283
Cell. 2020 Apr 16;181(2):325-345.e28
pubmed: 32302571
APL Bioeng. 2022 Apr 28;6(2):021503
pubmed: 35540725
Science. 2019 Jul 26;365(6451):342-347
pubmed: 31296649
Annu Rev Biophys. 2020 May 6;49:107-133
pubmed: 32004090
J Cell Biol. 2021 Mar 1;220(3):
pubmed: 33502444