Molecular requirements for the inter-subunit interaction and kinetochore recruitment of SKAP and Astrin
| Autor: | Alex C. Faesen, Stefan Raunser, Arsen Petrovic, Pim J Huis in 't Veld, Franz Herzog, Andrea Musacchio, Alexandra Friese, Daniel Prumbaum, Josef Fischböck |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Models Molecular Microtubule-associated protein Protein subunit Science Molecular Sequence Data General Physics and Astronomy Gene Expression Mitosis Cell Cycle Proteins Spindle Apparatus Microtubules General Biochemistry Genetics and Molecular Biology Article Protein Structure Secondary Chromosome segregation 03 medical and health sciences Microtubule Tubulin Chromosome Segregation Escherichia coli Humans Protein Interaction Domains and Motifs Amino Acid Sequence Kinetochores Multidisciplinary Binding Sites biology Kinetochore General Chemistry Recombinant Proteins Cell biology Spindle apparatus Protein Transport 030104 developmental biology biology.protein Protein Multimerization Biologie Microtubule-Associated Proteins Sequence Alignment HeLa Cells Protein Binding |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) |
| Popis: | Accurate chromosome segregation during cell division is crucial for propagating life and protects from cellular transformation. The SKAP:Astrin heterodimer localizes to spindle microtubules and to mature microtubule–kinetochore attachments during mitosis. Depletion of either subunit disrupts spindle structure and destabilizes kinetochore–microtubule attachments. Here, we identify molecular requirements for the inter-subunit interaction of SKAP and Astrin, and discuss requirements for their kinetochore recruitment. We also identify and characterize a microtubule-binding domain in SKAP, distinct from the SXIP motif that mediates end binding (EB) protein binding and plus end tracking, and show that it stimulates the growth-rate of microtubules, possibly through a direct interaction with tubulin. Mutations targeting this microtubule-binding domain impair microtubule plus-end tracking but not kinetochore targeting, and recapitulate many effects observed during depletion of SKAP. Collectively, our studies represent the first thorough mechanistic analysis of SKAP and Astrin, and significantly advance our functional understanding of these important mitotic proteins. SKAP and Astrin form a heterodimer that localizes to spindle microtubules and to mature microtubule-kinetochore attachments during mitosis. Here, the authors identify molecular requirements for the inter-subunit interaction of SKAP and Astrin and kinetochore recruitment. |
| Databáze: | OpenAIRE |
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