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Composition can buffer protein dynamics within liquid-like condensates

Stela Jelenic, Janos Bindics, Philipp Czermak, Balashankar R Pillai, Martine Ruer, Alex S Holehouse, Shambaditya Saha
doi: https://doi.org/10.1101/2022.05.16.492059
Stela Jelenic
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
2Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria
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Janos Bindics
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
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Philipp Czermak
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
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Balashankar R Pillai
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
2Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria
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Martine Ruer
3Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany
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Alex S Holehouse
4Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA
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Shambaditya Saha
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Dr. Bohr-Gasse 3, 1030 Vienna, Austria
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  • For correspondence: shambaditya.saha@imba.oeaw.ac.at
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Summary

Most non-membrane-bound compartments in cells that form via phase separation have complex composition. Phase separation of individual proteins that form these compartments has been well documented. However, we know relatively little about how the dynamics of individual proteins are modulated in multicomponent systems. Here, we used in vitro reconstitution and in vivo experiments to investigate how complex composition within a liquid-like ‘P granule’ compartment affects the dynamics of one of its scaffold proteins PGL-3. Using mutational analysis and biophysical perturbations, we generated PGL-3 constructs with reduced alpha-helicity that phase separate in vitro into condensates with widely varying dynamics. We use these PGL-3 constructs to show that introducing other P granule components buffers against large change of dynamics within liquid-like compartments. This dynamics-buffering effect is mediated by weak interactions among two or more components. Such dynamics-buffering may contribute to robust functional output of cellular liquid-like compartments.

Competing Interest Statement

Alex S. Holehouse is scientific advisor at Dewpoint Therapeutics.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 16, 2022.
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Composition can buffer protein dynamics within liquid-like condensates
Stela Jelenic, Janos Bindics, Philipp Czermak, Balashankar R Pillai, Martine Ruer, Alex S Holehouse, Shambaditya Saha
bioRxiv 2022.05.16.492059; doi: https://doi.org/10.1101/2022.05.16.492059
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Composition can buffer protein dynamics within liquid-like condensates
Stela Jelenic, Janos Bindics, Philipp Czermak, Balashankar R Pillai, Martine Ruer, Alex S Holehouse, Shambaditya Saha
bioRxiv 2022.05.16.492059; doi: https://doi.org/10.1101/2022.05.16.492059

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