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Figure 7. A sequential multi-target phosphorylation cascade by Mps1 promotes the assembly and activation of the Bub1–Mad1 scaffold.(A) Mps1 recognizes unattached kinetochores (KT) through its direct binding to the Ndc80 complex (Ndc80C). At kinetochores, Mps1 first phosphorylates Knl1 at multiple MELT motifs to recruit the Bub1–Bub3 complex (a). After Cdk1 phosphorylates Bub1 S459, Mps1 then phosphorylates Bub1 T461 (b). The doubly phosphorylated Bub1 conserved motif (CM) binds to and recruits the Mad1–C-Mad2 core complex. Mps1 then phosphorylates Mad1 at T716, and this phosphorylation enables Mad1 binding to Cdc20 (c). (B) The boxed region in (A) is magnified and shown with more molecular details here. The Mad1–C-Mad2 core complex bound to phosphorylated Bub1 CM can further recruit O-Mad2 and convert it to I-Mad2. The WD40 domain of Cdc20 is anchored to the Phe and KEN boxes of Bub1, whereas the N-terminal basic tail of Cdc20 is bound by the phosphorylated Mad1 CTD. This bipartite Cdc20-binding mode positions the MIM of Cdc20 close to I-Mad2, promoting the formation of the C-Mad2–Cdc20 complex. This binary complex can further bind to BubR1 (bound to Bub1 or from cytosol) to form MCC.DOI: http://dx.doi.org/10.7554/eLife.22513.012 Image published in: Ji Z et al. (2017) © 2017, Ji et al. This image is reproduced with permission of the journal and the copyright holder. This is an open-access article distributed under the terms of the Creative Commons Attribution license Larger Image Printer Friendly View

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