Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic {alpha}-helix

Aurora-A regulates the recruitment of TACC3 to the mitotic spindle through a phospho-dependent interaction with clathrin heavy chain (CHC). Here, we describe the structural basis of these interactions, mediated by three motifs in a disordered region of TACC3. A hydrophobic docking motif binds to a previously uncharacterized pocket on Aurora-A that is blocked in most kinases. Abrogation of the docking motif causes a delay in late mitosis, consistent with the cellular distribution of Aurora-A complexes. Phosphorylation of Ser558 engages a conformational switch in a second motif from a disordered state, needed to bind the kinase active site, into a helical conformation. The helix extends into a third, adjacent motif that is recognized by a helical-repeat region of CHC, not a recognized phospho-reader domain. This potentially widespread mechanism of phospho-recognition provides greater flexibility to tune the molecular details of the interaction than canonical recognition motifs that are dominated by phosphate binding.

Source: EMBO Journal - April 13, 2018 Category: Molecular Biology Authors: Burgess, S. G., Mukherjee, M., Sabir, S., Joseph, N., Gutierrez-Caballero, C., Richards, M. W., Huguenin-Dezot, N., Chin, J. W., Kennedy, E. J., Pfuhl, M., Royle, S. J., Gergely, F., Bayliss, R. Tags: Cell Adhesion, Polarity & Cytoskeleton, Cell Cycle, Structural Biology Articles Source Type: research