5ODT

Aurora-A in complex with TACC3

Summary for 5ODT

• Entry DOI: 10.2210/pdb5odt/pdb
• Descriptor: Aurora kinase A, Transforming acidic coiled-coil-containing protein 3, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• Functional Keywords: mitotic kinase, transferase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome : O14965; Cytoplasm : Q9Y6A5
• Total number of polymer chains: 2
• Total formula weight: 39125.17

Authors

Burgess, S.G.,Bayliss, R. (deposition date: 2017-07-06, release date: 2018-03-14, Last modification date: 2024-01-17)

Primary citation

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.
Mitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic alpha-helix.
EMBO J., 37:-, 2018

PubMed 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.

PubMed: 29510984
DOI: 10.15252/embj.201797902

Experimental method

X-RAY DIFFRACTION (2.021 Å)