Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure

Area of Science:

• Cell Biology
• Biophysics
• Structural Biology

Background:

• Biomolecular condensates are crucial for regulating cellular processes.
• The link between atomic-level features and condensate function is not well understood.

Purpose of the Study:

• To investigate the relationship between atomic features and condensate function using polar organizing protein Z (PopZ) as a model.
• To understand how PopZ's material properties and cellular functions are determined by its ultrastructure.

Main Methods:

• Cryo-electron tomography
• Biochemistry
• Single-molecule techniques
• Molecular dynamics simulations

Main Results:

• PopZ forms a hierarchical filamentous condensate.
• The helical domain promotes filamentation and condensation, while the disordered domain inhibits these processes.
• Conformational changes are phase-dependent, regulating interfilament contacts and client binding.

Conclusions:

• Established a multiscale framework connecting molecular interactions and ultrastructure to condensate material properties and cellular function.
• Demonstrated how PopZ's structure dictates its role in spatiotemporal regulation of cellular processes.