Structure and regulation of the microtubule plus-end tracking protein Kar9
| Autor: | Anil Kumar, Sandro M. Meier, Yves Barral, Ana-Maria Farcas, Cristina Manatschal, Michel O. Steinmetz |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Saccharomyces cerevisiae Proteins Cell division Myosin Heavy Chains Chemistry Protein Conformation 030302 biochemistry & molecular biology Nuclear Proteins Spindle Apparatus macromolecular substances Aster (cell biology) Microtubules Cell biology Spindle apparatus Microtubule plus-end 03 medical and health sciences Actin Cytoskeleton Structural Biology Microtubule Myosin Spectrin Molecular Biology Actin 030304 developmental biology |
| Zdroj: | Structure, 29 (11) |
| ISSN: | 0969-2126 |
| Popis: | In many eukaryotes, coordination of chromosome segregation with cell cleavage relies on the patterned interaction of specific microtubules with actin filaments through dedicated microtubule plus-end tracking proteins (+TIPs). However, how these +TIPs are spatially controlled is unclear. The yeast +TIP Kar9 drives one of the spindle aster microtubules along actin cables to align the mitotic spindle with the axis of cell division. Here, we report the crystal structure of Kar9's folded domain, revealing spectrin repeats reminiscent of the +TIPs MACF/ACF7/Shot and PRC1/Ase1. Point mutations abrogating spectrin-repeat-mediated dimerization of Kar9 reduced and randomized Kar9 distribution to microtubule tips, and impaired spindle positioning. Six Cdk1 sites surround the Kar9 dimerization interface. Their phosphomimetic substitution inhibited Kar9 dimerization, displaced Kar9 from microtubules, and affected its interaction with the myosin motor Myo2. Our results provide molecular-level understanding on how diverse cell types may regulate and pattern microtubule-actin interactions to orchestrate their divisions. ISSN:0969-2126 ISSN:1878-4186 |
| Databáze: | OpenAIRE |
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