Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure

Scholl, D.; Boyd, T.; Latham, A. P.; Salazar, A.; Khan, A.; Boeynaems, S.; Holehouse, A. S.; Lander, G. C.; Sali, A.; Park, D.; Deniz, A. A.; Lasker, K.

doi:10.1101/2024.12.27.630454

bioRxiv · 10.1101/2024.12.27.630454

Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure

Scholl, D.·Boyd, T.·Latham, A. P.·Salazar, A.·Khan, A.·Boeynaems, S.·Holehouse, A. S.·Lander, G. C.·Sali, A.·Park, D.·Deniz, A. A.·Lasker, K.

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Abstract

Biomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ) as a model system, revealing how its material properties and cellular function depend on its ultrastructure. We revealed PopZs hierarchical assembly into a filamentous condensate by integrating cryo-electron tomography, biochemistry, single-molecule techniques, and molecular dynamics simulations. The helical domain drives filamentation and condensation, while the disordered domain inhibits them. Phase-dependent conformational changes prevent interfilament contacts in the dilute phase and expose client binding sites in the dense phase. These findings establish a multiscale framework that links molecular interactions and condensate ultrastructure to macroscopic material properties that drive cellular function.

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Scholl, D., Boyd, T., Latham, A. P., Salazar, A., Khan, A., Boeynaems, S., Holehouse, A. S., Lander, G. C., Sali, A., Park, D., Deniz, A. A., Lasker, K.. 2024-12-28. Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure. https://doi.org/10.1101/2024.12.27.630454

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