Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.
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Authors
Burgess, Selena G
Mukherjee, Manjeet
Sabir, Sarah
Joseph, Nimesh
Gutiérrez-Caballero, Cristina
Richards, Mark W
Huguenin-Dezot, Nicolas
Chin, Jason W
Kennedy, Eileen J
Publication Date
2018-04-13Journal Title
EMBO J
ISSN
0261-4189
Publisher
EMBO
Volume
37
Issue
8
Language
English
Type
Article
This Version
VoR
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
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
Abstract
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.
Keywords
disorder–order transition, intrinsically disordered protein, phosphorylation, protein kinase, protein–protein interaction, Aurora Kinase A, Cell Line, Humans, Microtubule-Associated Proteins, Protein Conformation, alpha-Helical, Spindle Apparatus
Sponsorship
Cancer Research UK (CB4180)
Cancer Research UK (C14303/A17197)
Identifiers
External DOI: https://doi.org/10.15252/embj.201797902
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277840
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