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bioRxiv · 10.1101/2022.11.09.515846

Structures of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface

Zahm, J.·Jenni, S.·Harrison, S. C.
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Abstract

The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between spindle microtubules and centromere associated proteins during chromosome segregation. We used AlphaFold 2 to obtain structural predictions of the Ndc80 "loop" region and the Ndc80:Nuf2 globular head domains that interact with the Dam1 subunit of the decameric DASH/Dam1 complex (Dam1c). The predictions guided design of constructs that readily yielded crystal structures, essentially congruent with the predicted ones. The Ndc80 "loop" is a stiff, straight -helical "switchback" structure, and flexibility within the long Ndc80c rod occurs instead at a hinge point between the globular head and the loop. Conserved stretches of the Dam1 C terminus bind Ndc80c with a short helix followed by an extended segment such that phosphorylation of Dam1 serines 257, 265, and 292 by the mitotic kinase Ipl1/Aurora B can release this contact during error correction of mis-attached kinetochores. We integrate the structural results presented here into our current molecular model of the kinetochore-microtubule interface. The model illustrates how multiple interactions between Ndc80c, DASH/Dam1c and the microtubule lattice stabilize kinetochore attachments.

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Zahm, J., Jenni, S., Harrison, S. C.. 2022-11-09. Structures of the Ndc80 complex and its interactions at the yeast kinetochore-microtubule interface. https://doi.org/10.1101/2022.11.09.515846

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