Structural basis of Stu2 recruitment to yeast kinetochores
- Howard Hughes Medical Institute, Harvard Medical School, United States
- University of Utah School of Medicine, United States
Abstract
Chromosome segregation during cell division requires engagement of kinetochores of sister chromatids with microtubules emanating from opposite poles. As the corresponding microtubules shorten, these 'bioriented' sister kinetochores experience tension-dependent stabilization of microtubule attachments. The yeast XMAP215 family member and microtubule polymerase, Stu2, associates with kinetochores and contributes to tension-dependent stabilization in vitro. We show here that a C-terminal segment of Stu2 binds the four-way junction of the Ndc80 complex (Ndc80c) and that residues conserved both in yeast Stu2 orthologs and in their metazoan counterparts make specific contacts with Ndc80 and Spc24. Mutations that perturb this interaction prevent association of Stu2 with kinetochores, impair cell viability, produce biorientation defects, and delay cell cycle progression. Ectopic tethering of the mutant Stu2 species to the Ndc80c junction restores wild-type function in vivo. These findings show that the role of Stu2 in tension-sensing depends on its association with kinetochores by binding with Ndc80c.
Data availability
Diffraction data have been deposited in PDB under the accession code: 7KDF
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Structure of Stu2 Bound to dwarf Ndc80cProtein Data Bank, 7KDF.
Article and author information
Author details
Stephen C Harrison
Funding
Damon Runyon Cancer Research Foundation (Dale F. Frey Award for Breakthrough Scientists,29-18)
- Matthew P Miller
Howard Hughes Medical Institute
- Stephen C Harrison
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Zahm et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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