Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins

ELife
Tyler S HarmonRohit V Pappu

Abstract

Phase transitions of linear multivalent proteins control the reversible formation of many intracellular membraneless bodies. Specific non-covalent crosslinks involving domains/motifs lead to system-spanning networks referred to as gels. Gelation transitions can occur with or without phase separation. In gelation driven by phase separation multivalent proteins and their ligands condense into dense droplets, and gels form within droplets. System spanning networks can also form without a condensation or demixing of proteins into droplets. Gelation driven by phase separation requires lower protein concentrations, and seems to be the biologically preferred mechanism for forming membraneless bodies. Here, we use coarse-grained computer simulations and the theory of associative polymers to uncover the physical properties of intrinsically disordered linkers that determine the extent to which gelation of linear multivalent proteins is driven by phase separation. Our findings are relevant for understanding how sequence-encoded information in disordered linkers influences phase transitions of multivalent proteins.

References

Jan 1, 1988·Advances in Protein Chemistry·S K Burley, G A Petsko
Dec 12, 2002·Journal of the American Chemical Society·Joel P SchneiderJuliana Kretsinger
Sep 25, 2003·Journal of the American Chemical Society·Darrin J PochanLisa Haines
Jul 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·W P Jencks
Dec 13, 2006·Physical Review Letters·Emanuela BianchiFrancesco Sciortino
Apr 17, 2008·The Journal of Chemical Physics·Emanuela BianchiFrancesco Sciortino
May 29, 2008·Journal of Computational Chemistry·Andreas Vitalis, Rohit V Pappu
Jan 1, 2009·Annual Reports in Computational Chemistry·Andreas Vitalis, Rohit V Pappu
Mar 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Clifford P BrangwynneAnthony A Hyman
Jun 12, 2012·Cell·Stephanie C Weber, Clifford P Brangwynne
Dec 18, 2012·The Biochemical Journal·Albert H MaoRohit V Pappu
May 28, 2013·Current Opinion in Structural Biology·Marija BuljanM Madan Babu
Aug 1, 2013·Proceedings of the National Academy of Sciences of the United States of America·Rahul K Das, Rohit V Pappu
Nov 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·Scott L CrickRohit V Pappu
Nov 30, 2013·Nucleic Acids Research·Robert D FinnMarco Punta
Feb 26, 2015·The Journal of Cell Biology·ChangHwan LeeAmy S Gladfelter
Apr 13, 2015·Current Opinion in Structural Biology·Rahul K DasRohit V Pappu
May 6, 2015·Current Opinion in Cell Biology·Lian Zhu, Clifford P Brangwynne
Nov 11, 2015·Proceedings of the National Academy of Sciences of the United States of America·Sudeep BanjadeMichael K Rosen
Mar 1, 2016·Chemical Reviews·Veronika CsizmokJulie D Forman-Kay
May 4, 2016·Proceedings of the National Academy of Sciences of the United States of America·Rahul K DasRohit V Pappu
May 21, 2016·Cell·Louis-Philippe Bergeron-SandovalStephen W Michnick
May 24, 2016·Cell·Marina FericClifford P Brangwynne
Jun 4, 2016·Current Opinion in Structural Biology·Randal Halfmann
Jun 13, 2016·Trends in Cell Biology·David S W Protter, Roy Parker
Jul 5, 2016·Cell·Salman F BananiMichael K Rosen
Sep 8, 2016·ELife·Joshua R WheelerRoy Parker

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Citations

Apr 11, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Richard J Wheeler, Anthony A Hyman
Jan 19, 2018·Annual Review of Biophysics·Alex S Holehouse, Rohit V Pappu
Aug 8, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Katerina Cermakova, H Courtney Hodges
Aug 26, 2018·Proteomics·Brett JanisMichael A Menze
Sep 16, 2018·Proceedings of the National Academy of Sciences of the United States of America·Gregory L DignonJeetain Mittal
Jan 6, 2018·Science·Titus M FranzmannSimon Alberti
Dec 28, 2018·Chemistry : a European Journal·Emily P BentleyAshok A Deniz
Apr 20, 2019·Traffic·Tobias WunderOliver Mueller-Cajar
Sep 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Archishman GhoshHuan-Xiang Zhou
Jan 7, 2020·PLoS Genetics·Bharath SaravananDimple Notani
Jan 4, 2020·Molecular Biology and Evolution·Joshua S MacCreadyAnthony G Vecchiarelli
Mar 8, 2019·Angewandte Chemie·Bryce E Ackermann, Galia T Debelouchina
Sep 29, 2019·Nature Communications·Samuel J BlackRichard T Pomerantz
Feb 1, 2020·Annual Review of Biophysics·Jeong-Mo ChoiRohit V Pappu
Oct 22, 2019·PLoS Computational Biology·Jeong-Mo ChoiRohit V Pappu
May 24, 2020·Wiley Interdisciplinary Reviews. RNA·Nisansala S MuthunayakeJared M Schrader
Jun 3, 2020·ELife·Srivastav Ranganathan, Eugene I Shakhnovich
Jun 26, 2020·Soft Matter·J C ShillcockJ H Ipsen
Jul 7, 2020·Acta Crystallographica. Section D, Structural Biology·Shengyang JinYong Gui Gao
Aug 12, 2020·Cellular and Molecular Life Sciences : CMLS·S PankivskyiL Hamon
Aug 13, 2020·RNA Biology·Ahyun SonBaik L Seong
Aug 22, 2020·Physical Chemistry Chemical Physics : PCCP·Milan Kumar Hazra, Yaakov Levy
Sep 12, 2018·Annual Review of Microbiology·Erin M Langdon, Amy S Gladfelter
Oct 17, 2018·Nature Materials·Stefan RobertsAshutosh Chilkoti
Mar 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·Steven BoeynaemsAaron D Gitler
Apr 6, 2019·Annual Review of Biophysics·Lindsay B CaseMichael K Rosen
May 16, 2019·ELife·Christoph WeberL Mahadevan
Aug 21, 2019·Annual Review of Genetics·Simon Alberti, Dorothee Dormann
Oct 28, 2019·International Journal of Molecular Sciences·Aneta Tarczewska, Beata Greb-Markiewicz
Jun 3, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jorge R EspinosaRosana Collepardo-Guevara
Jul 28, 2019·Nature Communications·Wenqin BaiFuzhong Zhang
Mar 28, 2020·Nature Communications·Bin XuNed S Wingreen
Dec 25, 2019·Physical Review. E·Nicholas A S RobichaudStefan Wallin
Jan 9, 2020·Annual Review of Biophysics·Wade F ZenoJeanne C Stachowiak
Aug 23, 2020·International Journal of Molecular Sciences·Alain A M André, Evan Spruijt
Apr 20, 2019·Frontiers in Molecular Biosciences·Karina K NakashimaEvan Spruijt
Aug 4, 2019·Protein Engineering, Design & Selection : PEDS·Megan C CohanRohit V Pappu
Mar 9, 2019·Science·Erik W Martin, Tanja Mittag

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Software Mentioned

PANTHER
ABSINTH
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CAMPARI

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