The human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments
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Abstract:
The accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule ends. The strength of this attachment is fundamental to the kinetochore function of harnessing the energy from microtubule disassembly for chromosome movement. The human Ska complex and Ndc80 complex are outer kinetochore components that bind microtubules and are required to fully strengthen kinetochore microtubule attachments in vivo. It is unclear whether the Ska complex acts directly to increase kinetochore microtubule attachment strength or whether it acts indirectly as a regulator. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips as well as strengthens Ndc80 complex microtubule end attachments and increases the switching dynamics of Ndc80 complex bound microtubules. Crosslinking mass spectrometry shows the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminus and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule binding domain or the Ska3 C-terminus prevents Ska complex from strengthening Ndc80 complex based attachments. Together our results indicate that the Ska complex can directly strengthen the kinetochore microtubule interface and regulate microtubule tip dynamics by forming an additional connection from the Ndc80 complex to the microtubule.
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Notes:
This page provides public access to data associated with Helgeson et al. (2018)