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The filamentous ultrastructure of the PopZ condensate is required for its cellular function

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Scholl, Daniel, Boyd, Tumara, Latham, Andrew P., Salazar, Alexandra, Khan, Asma M. A. M., Boeynaems, Steven, Holehouse, Alex S., Lander, Gabriel C., Sali, Andrej, Park, Donghyun, Deniz, Ashok A., Lasker, Keren·2026·Nature Structural & Molecular Biology
DOI 10.1038/s41594-025-01742-yPMC PMC11703246

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Abstract

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. M. A. M., 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
ORCID
Venue
Nature Structural & Molecular Biology
Publisher
Springer Science and Business Media LLC
Published
2026-02-02
Volume
33
Issue
3
Pages
420-432
ISSN
  • 1545-9985 (ISSN-L)
  • 1545-9993
DOI
10.1038/s41594-025-01742-y
PMC
PMC11703246
OpenAlex
W7127082149
Cited by
14
References
5
Citations by year
2026: 12
FWCI
24.80
Type
journal article
Language
en
Open access
Licence
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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