The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems

Keren Lasker (), Steven Boeynaems, Vinson Lam, Daniel Scholl, Emma Stainton, Adam Briner, Maarten Jacquemyn, Dirk Daelemans, Ashok Deniz, Elizabeth Villa, Alex S. Holehouse, Aaron D. Gitler () and Lucy Shapiro ()
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Keren Lasker: Stanford University School of Medicine
Steven Boeynaems: Stanford University School of Medicine
Vinson Lam: University of California San Diego
Daniel Scholl: The Scripps Research Institute
Emma Stainton: Stanford University School of Medicine
Adam Briner: The University of Queensland
Maarten Jacquemyn: KU Leuven
Dirk Daelemans: KU Leuven
Ashok Deniz: The Scripps Research Institute
Elizabeth Villa: University of California San Diego
Alex S. Holehouse: Washington University in St. Louis
Aaron D. Gitler: Stanford University School of Medicine
Lucy Shapiro: Stanford University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells.

Date: 2022
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DOI: 10.1038/s41467-022-33221-z

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