PreprintCited by 14Protein Structure and DynamicsRNA Research and SplicingMicrotubule and mitosis dynamics

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Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure

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Preprint — published as 10.1038/s41594-025-01742-y · Paper page

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 PopZ’s 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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Metadata

Authors
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.
Affiliations
  • Scripps Research Institute (US)
  • University of California, San Francisco (US)
  • Baylor College of Medicine (US)
  • Washington University in St. Louis (US)
Corresponding author
  • Park, Donghyun
  • Deniz, Ashok A.
  • Lasker, Keren
Venue
Nature Structural & Molecular Biology
Publisher
openRxiv
Published
2024-12-28
Volume
33
Issue
3
Pages
420-432
ISSN
1545-9985 (ISSN-L)
OpenAlex
W7127082149
Cited by
14
References
1
Citations by year
2026: 12 · 2025: 2
FWCI
24.63
Type
journal article
Language
en
Open access
Locations
  • Nature Structural & Molecular Biology (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
Funders
  • National Institutes of Health (1s10od032467-01)
  • National Institute of General Medical Sciences (R01GM083960, F32GM150243, R35GM130375)
  • National Institute of Neurological Disorders and Stroke (DP2NS142714, R01NS095892)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
PopZ, biomolecular condensates, helical domain, intrinsically disordered regions, phase separation, cell growth

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