Phase separation of a microtubule plus-end tracking protein into a fluid fractal network
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 separat...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56468-8 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mateusz P. Czub |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c265bc0116364fd884e04b2afa43c196 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-c265bc0116364fd884e04b2afa43c1962025-02-02T12:33:38ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-56468-8Phase separation of a microtubule plus-end tracking protein into a fluid fractal networkMateusz P. Czub0Federico Uliana1Tarik Grubić2Celestino Padeste3Kathryn A. Rosowski4Charlotta Lorenz5Eric R. Dufresne6Andreas Menzel7Ioannis Vakonakis8Urs Gasser9Michel O. Steinmetz10PSI Center for Life SciencesInstitute of Biochemistry, Department of Biology, ETH ZürichPSI Center for Life SciencesPSI Center for Life SciencesDepartment of Materials, ETH ZürichDepartment of Materials, ETH ZürichDepartment of Materials, ETH ZürichPSI Center for Photon ScienceDepartment of Biochemistry, University of OxfordPSI Center for Neutron and Muon SciencesPSI Center for Life SciencesAbstract 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.https://doi.org/10.1038/s41467-025-56468-8 |
| spellingShingle | 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 Phase separation of a microtubule plus-end tracking protein into a fluid fractal network Nature Communications |
| title | Phase separation of a microtubule plus-end tracking protein into a fluid fractal network |
| title_full | Phase separation of a microtubule plus-end tracking protein into a fluid fractal network |
| title_fullStr | Phase separation of a microtubule plus-end tracking protein into a fluid fractal network |
| title_full_unstemmed | Phase separation of a microtubule plus-end tracking protein into a fluid fractal network |
| title_short | Phase separation of a microtubule plus-end tracking protein into a fluid fractal network |
| title_sort | phase separation of a microtubule plus end tracking protein into a fluid fractal network |
| url | https://doi.org/10.1038/s41467-025-56468-8 |
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