1ol6
STRUCTURE OF UNPHOSPHORYLATED D274N MUTANT OF AURORA-A
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OverviewOverview
Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It, is activated by phosphorylation and by the microtubule-associated protein, TPX2, which also localizes the kinase to spindle microtubules. We have, uncovered the molecular mechanism of Aurora-A activation by determining, crystal structures of its phosphorylated form both with and without a 43, residue long domain of TPX2 that we identified as fully functional for, kinase activation and protection from dephosphorylation. In the absence of, TPX2, the Aurora-A activation segment is in an inactive conformation, with, the crucial phosphothreonine exposed and accessible for deactivation., Binding of TPX2 triggers no global conformational changes in the kinase, but pulls on the activation segment, swinging the phosphothreonine into a, buried position and locking the active conformation. The recognition, between Aurora-A and TPX2 resembles that between the cAPK catalytic core, and its flanking regions, suggesting this molecular mechanism may be a, recurring theme in kinase regulation.
DiseaseDisease
Known diseases associated with this structure: Colon cancer, susceptibility to OMIM:[603072]
About this StructureAbout this Structure
1OL6 is a Single protein structure of sequence from Homo sapiens with ATP as ligand. Active as Transferred entry: 2.7.11.1, with EC number 2.7.1.37 Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structural basis of Aurora-A activation by TPX2 at the mitotic spindle., Bayliss R, Sardon T, Vernos I, Conti E, Mol Cell. 2003 Oct;12(4):851-62. PMID:14580337
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