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Phase separation of a microtubule plus-end tracking protein into a fluid fractal network

Author

Listed:
  • Mateusz P. Czub

    (PSI Center for Life Sciences)

  • Federico Uliana

    (ETH Zürich
    Johannes Gutenberg University of Mainz)

  • Tarik Grubić

    (PSI Center for Life Sciences)

  • Celestino Padeste

    (PSI Center for Life Sciences)

  • Kathryn A. Rosowski

    (ETH Zürich
    F. Hoffmann-La Roche Ltd)

  • Charlotta Lorenz

    (ETH Zürich
    University of Zurich)

  • Eric R. Dufresne

    (ETH Zürich
    Cornell University)

  • Andreas Menzel

    (PSI Center for Photon Science)

  • Ioannis Vakonakis

    (University of Oxford
    Microbial Development)

  • Urs Gasser

    (PSI Center for Neutron and Muon Sciences)

  • Michel O. Steinmetz

    (PSI Center for Life Sciences
    Biozentrum)

Abstract

Microtubule plus-end tracking proteins (+TIPs) participate in nearly all microtubule-based cellular processes and have recently been proposed to function as liquid condensates. However, their formation and internal organization remain poorly understood. Here, we have study the phase separation of Bik1, a CLIP-170 family member and key +TIP involved in budding yeast cell division. Bik1 is a dimer with a rod-shaped conformation primarily defined by its central coiled-coil domain. Its liquid condensation likely involves the formation of higher-order oligomers that phase separate in a manner dependent on the protein’s N-terminal CAP-Gly domain and C-terminal EEY/F-like motif. This process is accompanied by conformational rearrangements in Bik1, leading to at least a two-fold increase in multivalent interactions between its folded and disordered domains. Unlike classical liquids, Bik1 condensates exhibit a heterogeneous, fractal supramolecular structure with protein- and solvent-rich regions. This structural evidence supports recent percolation-based models of biomolecular condensates. Together, our findings offer insights into the structure, dynamic rearrangement, and organization of a complex, oligomeric, and multidomain protein in both dilute and condensed states. Our experimental framework can be applied to other biomolecular condensates, including more complex +TIP networks.

Suggested Citation

  • Mateusz P. Czub & Federico Uliana & Tarik Grubić & Celestino Padeste & Kathryn A. Rosowski & Charlotta Lorenz & Eric R. Dufresne & Andreas Menzel & Ioannis Vakonakis & Urs Gasser & Michel O. Steinmetz, 2025. "Phase separation of a microtubule plus-end tracking protein into a fluid fractal network," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56468-8
    DOI: 10.1038/s41467-025-56468-8
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