Figure 2. Molecular architecture of the kinetochore.

(a) Architecture of a single microtubule-kinetochore attachment site. For clarity only one CCAN (pink) and the associated molecules is shown (see Fig. 3 for extension of models to multi-subunit kinetochores). All molecules are drawn to scale based on known structural biology, length of coiled-coil sequences or length of disordered regions. The relative position of molecules is informed by the measured Euclidian distances between the average positions of two labelled proteins in a population of kinetochores (see (213)) and/or known binding interfaces. Key features: Red circles donate known contact points between a protein and the microtubule. Flexible linkers connect CCAN to KMN (1) extended coiled-coil elements span subassembly II to sub-assembly III (CenpF, CenpE, Mad1). Detachment of microtubules triggers a switch in composition and architecture: SAC factors (yellow) including Mad1:Mad2 load on Bub1-Bub3 that are bound on the Knl1 phospho-domain (black dots) which causes rearrangement of NDC80C as they jack-knife and loose order (2). Other factors that load or leave are designated by green and red dotted arrows respectively. Not all factors are shown. Scale bar = 10 nm.

(b) Dynamic remodelling of kinetochores: at the start of mitosis kinetochores have not yet established amphitelic attachment and the SAC (yellow molecule) is actively delaying anaphase onset. In humans, there is expansion of subassembly III (green) into the corona founded on self-assembly of RZZ (light green). As end on attachments form, the corona (and SAC) is disassembled in part by dynein-driven stripping of corona cargoes. This leaves residual corona molecules spanning to subassembly II. Stretching of linkers separates subassembly I (pink) and II (blue ) when under tension while there are conformational changes within the latter.