Figure 7. Knl1 MELTs and the KI1 and KI2 motifs in SAC signaling.
(a) A schematic depiction of Knl1 with its 19 Met-Glu-Leu-Thr (MELT) repeats. The activity of each MELT, as defined by the ability of the MELT to recruit the Bub3:Bub1 complex for SAC signaling, corresponds to a color gradient (the darker the more active).145,146 The strength of the Bub3:MELT interaction is also depicted by the arrow length (the shorter the stronger the binding). (b) A close-up of the N-terminus of Knl1 where MELT1 is immediately proceeded by the KI1 and KI2 motifs which bind to the tetratricopeptide repeat (TPR) lobes of Bub1 and BubR1, respectively. This mechanism enhances Bub1/BubR1 recruitment and is unique to some metazoans including humans. (c) Strong MELT motif activity requires sequential multisite phosphorylation of the Knl1:Bub3 interface by Mps1. Mps1 first phosphorylates the threonine MELT residue (MELpT) which enhances Mps1 phosphorylation at the SHT motif. Strong recruiters of Bub3:Bub1 require the SHT motif to enhance the Bub3:MELT interaction.