TY - JOUR TI - Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling AU - Primorac, Ivana AU - Weir, John R AU - Chiroli, Elena AU - Gross, Fridolin AU - Hoffmann, Ingrid AU - van Gerwen, Suzan AU - Ciliberto, Andrea AU - Musacchio, Andrea A2 - Pines, Jon VL - 2 PY - 2013 DA - 2013/09/24 SP - e01030 C1 - eLife 2013;2:e01030 DO - 10.7554/eLife.01030 UR - https://doi.org/10.7554/eLife.01030 AB - Regulation of macromolecular interactions by phosphorylation is crucial in signaling networks. In the spindle assembly checkpoint (SAC), which enables errorless chromosome segregation, phosphorylation promotes recruitment of SAC proteins to tensionless kinetochores. The SAC kinase Mps1 phosphorylates multiple Met-Glu-Leu-Thr (MELT) motifs on the kinetochore subunit Spc105/Knl1. The phosphorylated MELT motifs (MELTP) then promote recruitment of downstream signaling components. How MELTP motifs are recognized is unclear. In this study, we report that Bub3, a 7-bladed β-propeller, is the MELTP reader. It contains an exceptionally well-conserved interface that docks the MELTP sequence on the side of the β-propeller in a previously unknown binding mode. Mutations targeting the Bub3 interface prevent kinetochore recruitment of the SAC kinase Bub1. Crucially, they also cause a checkpoint defect, showing that recognition of phosphorylated targets by Bub3 is required for checkpoint signaling. Our data provide the first detailed mechanistic insight into how phosphorylation promotes recruitment of checkpoint proteins to kinetochores. KW - spindle assembly checkpoint KW - kinetochore KW - Bub3 KW - Bub1 KW - Mad3 KW - Knl1 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -