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Abstract:
Kinetochores are proteinaceous assemblies that mediate the interaction
of chromosomes with the mitotic spindle. The 180 kDa Ndc80 complex is a
direct point of contact between kinetochores and microtubules. Its four
subunits contain coiled coils and form an elongated rod structure with
functional globular domains at either end. We crystallized an engineered
"bonsai'' Ndc80 complex containing a shortened rod domain but retaining
the globular domains required for kinetochore localization and
microtubule binding. The structure reveals a microtubule-binding
interface containing a pair of tightly interacting calponin-homology
(CH) domains with a previously unknown arrangement. The interaction with
microtubules is cooperative and predominantly electrostatic. It involves
positive charges in the CH domains and in the N-terminal tail of the
Ndc80 subunit and negative charges in tubulin C-terminal tails and is
regulated by the Aurora B kinase. We discuss our results with reference
to current models of kinetochore-microtubule attachment and centromere
organization.
