1ol6: Difference between revisions
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==Overview== | ==Overview== | ||
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. | 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. | ||
==Disease== | |||
Known diseases associated with this structure: Colon cancer, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603072 603072]] | |||
==About this Structure== | ==About this Structure== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:34:13 2007'' | ||