生物
主轴装置
有丝分裂
细胞生物学
极光激酶B
微管
磷酸化
脱磷
蛋白激酶结构域
激酶
极光激酶
极光A激酶
蛋白激酶A
细胞周期
生物物理学
生物化学
磷酸酶
细胞分裂
细胞
基因
突变体
作者
Richard Bayliss,Teresa Sardón,Isabelle Vernos,Elena Conti
出处
期刊:Molecular Cell
[Elsevier]
日期:2003-10-01
卷期号:12 (4): 851-862
被引量:538
标识
DOI:10.1016/s1097-2765(03)00392-7
摘要
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.
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