Abstract
The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures (‘straight’ during microtubule polymerization and ‘curved’ during microtubule depolymerization) is an essential requirement for accurate chromosome segregation. Here we show that the kinetochore-associated Ska complex interacts with tubulin monomers via the carboxy-terminal winged-helix domain of Ska1, providing the structural basis for the ability to bind both straight and curved microtubule structures. This contrasts with the Ndc80 complex, which binds straight microtubules by recognizing the dimeric interface of tubulin. The Ska1 microtubule-binding domain interacts with tubulins using multiple contact sites that allow the Ska complex to bind microtubules in multiple modes. Disrupting either the flexibility or the tubulin contact sites of the Ska1 microtubule-binding domain perturbs normal mitotic progression, explaining the critical role of the Ska complex in maintaining a firm grip on dynamic microtubules.
Highlights
The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures (‘straight’ during microtubule polymerization and ‘curved’ during microtubule depolymerization) is an essential requirement for accurate chromosome segregation
These observations suggest that Ska1133–255 is the major MT-binding element within the Ska complex, which, on dimerization, can bind MTs more efficiently
With MT-binding domains (MTBDs) symmetrically positioned at both ends of the dimer, the Ska complex appears to exert its function via a different mechanism
Summary
The ability of kinetochores (KTs) to maintain stable attachments to dynamic microtubule structures (‘straight’ during microtubule polymerization and ‘curved’ during microtubule depolymerization) is an essential requirement for accurate chromosome segregation. A recently reported nuclear magnetic resonance (NMR) structure of the Caenorhabditis elegans Ska1– MTBD revealed the involvement of a winged-helix domain in MT recognition[31] At this point, information on how the Ska complex interacts with MTs is crucial to understand the role of the Ska complex in potentially coupling MT dynamics and chromosome segregation. We show that the Ska complex, unlike the Ndc[80] complex, can bind tubulin monomers in different orientations via its multiple MT contact sites, allowing it to recognize MTs in a conformation-independent manner
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