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Published in final edited form as: Nat Rev Mol Cell Biol. 2014 Oct 10;15(11):736–747. doi: 10.1038/nrm3888

(A) Interacting regions of kinetochore and checkpoint proteins are depicted. Lines between regions indicate established interactions, and phosphoregulated interactions are shown in red. BubR1/Mad3 domains vary by organism with the pseudokinase domain absent from some lineages⁵⁷. Structures have been determined for interactions of Bub1-Bub3 and BubR1/Mad3-Bub3⁵⁸, Bub1/3-Knl1⁵¹, BubR1/Mad3-Knl1⁷², BubR1/Mad3-Mad2^32,148 and Mad1/2¹⁴⁹. MELT-like repeats exhibit poor sequence-level conservation and repeat numbers vary from 2 in some fungi and plants to 27 in Xenopus tropicalis^57,70. Note that a single MELT-like motif interacts with three WD40 domains⁵¹. C-helix, RLK, CD1, and Bub3-binding regions are all required for the checkpoint. RLK: A Mad1 motif required for Bub1 association⁸⁶. C-helix: the Mad1 C-terminal helix. CD1: “conserved domain 1” of Bub1^90,93. TPR and WD40 are common protein domains. Diagrams are oriented with N-termini on the left. (B) Hypothetical BubR1 kinetochore binding mechanisms. (i) The KI2 motif of Knl1 interacts directly with BubR1, possibly facilitating recruitment of a single BubR1 molecule^47,63,70. (ii) Bub1 may also recruit BubR1, possibly through a Bub1-BubR1 interaction. Bub3 that is associated with BubR1 at the kinetochore may therefore be available for other interactions⁶³. Bub1:BubR1 stoichiometry at the kinetochore has not been systematically analyzed.

(A) Interacting regions of kinetochore and checkpoint proteins are depicted. Lines between regions indicate established interactions, and phosphoregulated interactions are shown in red. BubR1/Mad3 domains vary by organism with the pseudokinase domain absent from some lineages⁵⁷. Structures have been determined for interactions of Bub1-Bub3 and BubR1/Mad3-Bub3⁵⁸, Bub1/3-Knl1⁵¹, BubR1/Mad3-Knl1⁷², BubR1/Mad3-Mad2^32,148 and Mad1/2¹⁴⁹. MELT-like repeats exhibit poor sequence-level conservation and repeat numbers vary from 2 in some fungi and plants to 27 in Xenopus tropicalis^57,70. Note that a single MELT-like motif interacts with three WD40 domains⁵¹. C-helix, RLK, CD1, and Bub3-binding regions are all required for the checkpoint. RLK: A Mad1 motif required for Bub1 association⁸⁶. C-helix: the Mad1 C-terminal helix. CD1: “conserved domain 1” of Bub1^90,93. TPR and WD40 are common protein domains. Diagrams are oriented with N-termini on the left. (B) Hypothetical BubR1 kinetochore binding mechanisms. (i) The KI2 motif of Knl1 interacts directly with BubR1, possibly facilitating recruitment of a single BubR1 molecule^47,63,70. (ii) Bub1 may also recruit BubR1, possibly through a Bub1-BubR1 interaction. Bub3 that is associated with BubR1 at the kinetochore may therefore be available for other interactions⁶³. Bub1:BubR1 stoichiometry at the kinetochore has not been systematically analyzed.