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

Publication Type:

Journal Article


Open Biol, Volume 13, Issue 3, p.220378 (2023)


Aurora Kinase B, Cell Cycle Proteins, Centromere, Furylfuramide, Kinetochores, Microtubule-Associated Proteins, Microtubules, Nuclear Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins


<p>The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between mitotic spindle microtubules and centromere-associated proteins. We used AlphaFold 2 (AF2) to obtain predictions of the Ndc80 &#39;loop&#39; structure and of the Ndc80 : Nuf2 globular head domains that interact with the Dam1 subunit of the heterodecameric DASH/Dam1 complex (Dam1c). The predictions guided design of crystallizable constructs, with structures close to the predicted ones. The Ndc80 &#39;loop&#39; is a stiff, α-helical &#39;switchback&#39; structure; AF2 predictions and positions of preferential cleavage sites indicate that flexibility within the long Ndc80c rod occurs instead at a hinge closer to the globular head. Conserved stretches of the Dam1 C terminus bind Ndc80c such that phosphorylation of Dam1 serine residues 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.</p>

8G0P (Ndc80c loop) and 8G0Q (Ndc80:Dam1-Nuf2)