The structural basis of the multi-step allosteric activation of Aurora B kinase.
The structural basis of the multi-step allosteric activation of Aurora B kinase.
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DOI：
10.7554/elife.85328
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发表时间：
2023-05-25
期刊：
影响因子：
7.7
通讯作者：
Sekulic N
中科院分区：
文献类型：
--
作者：
Segura-Peña D;Hovet O;Gogoi H;Dawicki-McKenna J;Hansen Wøien SM;Carrer M;Black BE;Cascella M;Sekulic N
Aurora B与IN-box（INCENP的C-末端部分）一起形成酶复合物，确保忠实的细胞分裂。[Aurora B/IN-盒]复合物通过Aurora B激活环和IN-盒中的自磷酸化激活，但尚不清楚这些磷酸化如何激活酶。我们使用实验和计算研究相结合的方法来研究磷酸化对[Aurora B/IN-box]分子动力学和结构的影响。此外，我们产生了部分磷酸化的中间体，以独立地分析每个磷酸化的贡献。我们发现Aurora和IN-box的动力学是相互关联的，并且IN-box根据酶复合物的磷酸化状态起着积极和消极的调节作用。Aurora B激活环中的磷酸化发生在分子内，并为酶复合物的激活做好准备，但两个磷酸化位点协同作用地负责完全的酶活性。
Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] complex is activated by autophosphorylation in the Aurora B activation loop and in IN-box, but it is not clear how these phosphorylations activate the enzyme. We used a combination of experimental and computational studies to investigate the effects of phosphorylation on the molecular dynamics and structure of [Aurora B/IN-box]. In addition, we generated partially phosphorylated intermediates to analyze the contribution of each phosphorylation independently. We found that the dynamics of Aurora and IN-box are interconnected, and IN-box plays both positive and negative regulatory roles depending on the phosphorylation status of the enzyme complex. Phosphorylation in the activation loop of Aurora B occurs intramolecularly and prepares the enzyme complex for activation, but two phosphorylated sites are synergistically responsible for full enzyme activity.
DOI：
10.1016/j.jasms.2009.05.017
发表时间：
2009-10
影响因子：
3.2
作者：
Chitta RK;Rempel DL;Gross ML
通讯作者：
Gross ML
DOI：
10.1021/jasms.1c00271
发表时间：
2022-03-02
影响因子：
3.2
作者：
Tomlinson, Lauren J.;Batchelor, Matthew;Sarsby, Joscelyn;Byrne, Dominic P.;Brownridge, Philip J.;Bayliss, Richard;Eyers, Patrick A.;Eyers, Claire E.
通讯作者：
Eyers, Claire E.