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Mechanisms of active regulation of biomolecular condensates

View ORCID ProfileJohannes Söding, View ORCID ProfileDavid Zwicker, View ORCID ProfileSalma Sohrabi-Jahromi, Marc Boehning, Jan Kirschbaum
doi: https://doi.org/10.1101/694406
Johannes Söding
1Quantitative Biology & Bioinformatics and, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany
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  • For correspondence: soeding@mpibpc.mpg.de
David Zwicker
2Max-Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany
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Salma Sohrabi-Jahromi
1Quantitative Biology & Bioinformatics and, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany
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Marc Boehning
3Department of Molecular Biology, Max-Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen, Germany
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Jan Kirschbaum
2Max-Planck Institute for Dynamics and Self-Organization, Am Faßberg 17, 37077 Göttingen, Germany
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Abstract

Liquid-liquid phase separation is a key organizational principle in eukaryotic cells, on par with intracellular membranes. It allows cells to concentrate specific proteins into condensates, increasing reaction rates and achieving switch-like regulation. However, it is unclear how cells trigger condensate formation or dissolution and regulate their sizes. We predict from first principles two mechanisms of active regulation by post-translational modifications such as phosphorylation: In enrichment-inhibition, the regulating modifying enzyme enriches in condensates and the modifications of proteins inhibit their interactions. Stress granules, Cajal bodies, P granules, splicing speckles, and synapsin condensates obey this model. In localization-induction, condensates form around an immobilized modifying enzyme, whose modifications strengthen protein interactions. Spatially targeted condensates formed during transmembrane signaling, microtubule assembly, and actin polymerization conform to this model. The two models make testable predictions that can guide studies into the many emerging roles of biomolecular condensates.

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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 July 06, 2019.
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Mechanisms of active regulation of biomolecular condensates
Johannes Söding, David Zwicker, Salma Sohrabi-Jahromi, Marc Boehning, Jan Kirschbaum
bioRxiv 694406; doi: https://doi.org/10.1101/694406
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Mechanisms of active regulation of biomolecular condensates
Johannes Söding, David Zwicker, Salma Sohrabi-Jahromi, Marc Boehning, Jan Kirschbaum
bioRxiv 694406; doi: https://doi.org/10.1101/694406

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