Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.
Burgess, Selena G
Richards, Mark W
Kennedy, Eileen J
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Burgess, S. G., Mukherjee, M., Sabir, S., Joseph, N., Gutiérrez-Caballero, C., Richards, M. W., Huguenin-Dezot, N., et al. (2018). Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.. EMBO J, 37 (8) https://doi.org/10.15252/embj.201797902
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.
Cell Line, Humans, Microtubule-Associated Proteins, Spindle Apparatus, Aurora Kinase A, Protein Conformation, alpha-Helical
Cancer Research UK (CB4180)
Cancer Research UK (C14303/A17197)
External DOI: https://doi.org/10.15252/embj.201797902
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277840
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/