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

作者：Burgess Selena G; Mukherjee Manjeet; Sabir Sarah; Joseph Nimesh; Gutierrez Caballero Cristina; Richards Mark W; Huguenin Dezot Nicolas; Chin Jason W; Kennedy Eileen J; Pfuhl Mark; Royle Stephen J; Gergely Fanni; Bayliss Richard^*

来源：The EMBO Journal, 2018, 37(8): UNSP e97902.

DOI：10.15252/embj.201797902

• disorder-order transition
• intrinsically disordered protein
• phosphorylation
• protein kinase
• protein-protein interaction

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.

• 出版日期2018-4-13