Duncan NRI Faculty and Staff Publications

Language

English

Publication Date

3-1-2026

Journal

Nature Structural & Molecular Biology

DOI

10.1038/s41594-025-01742-y

PMID

41629604

PMCID

PMC12999525

PubMedCentral® Posted Date

2-2-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Biomolecular condensates have key roles in regulating 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). Here, we revealed hierarchical assembly of PopZ into a filamentous condensate by integrating cryo-electron tomography, biochemistry, single-molecule techniques and molecular dynamics simulations. The PopZ helical domain drives filamentation and condensation, while the disordered region inhibits them. Phase-dependent conformational changes prevent interfilament contacts in the dilute phase and expose client-binding sites in the dense phase. Perturbing filament formation in vitro alters the dynamics of scaffold and client proteins and the condensate's wetting behavior. In cells, perturbing either filament formation or the ability of filaments to condense impairs PopZ function and leads to growth phenotypes. These findings establish a multiscale framework linking molecular interactions and condensate ultrastructure to cellular function.

Keywords

Cryoelectron Microscopy, Molecular Dynamics Simulation, Electron Microscope Tomography, Biomolecular Condensates, Escherichia coli Proteins, Escherichia coli, Cellular microbiology, Molecular biophysics, Cell division, Cryoelectron tomography

Published Open-Access

yes

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