Dynamics-Driven Allostery in Protein Kinases.
Dynamics-Driven Allostery in Protein Kinases.
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DOI：
10.1016/j.tibs.2015.09.002
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发表时间：
2015-11
影响因子：
13.8
通讯作者：
Taylor SS
中科院分区：
文献类型：
--
作者：
Kornev AP;Taylor SS
蛋白激酶具有非常动态的结构，并且它们的功能强烈地依赖于它们的动态状态。活性激酶揭示了一种动态模式，其残基聚集成以µs-ms时间尺度移动的半刚性群落。以前检测到的疏水刺作为社区之间的连接器。社区不遵循激酶核心或其二级结构元件的传统子域结构。相反，它们是围绕主要职能单位组织的。群落的整合依赖于疏水棘的组装和激活环的磷酸化。单个突变可以显著破坏动态基础结构，从而干扰在整个分子中传播的长距离变构信号传导。动力学被认为是蛋白激酶变构调节的基本机制。
Protein kinases have very dynamic structures and their functionality strongly depends on their dynamic state. Active kinases reveal a dynamic pattern with residues clustering into semirigid communities that move in µs-ms timescale. Previously detected hydrophobic spines serve as connectors between communities. Communities do not follow the traditional subdomain structure of the kinase core or its secondary structure elements. Instead they are organized around main functional units. Integration of the communities depends on the assembly of the hydrophobic spine and phosphorylation of the activation loop. Single mutations can significantly disrupt the dynamic infrastructure and thereby interfere with long distance allosteric signaling that propagates throughout the whole molecule. Dynamics is proposed to be the underlying mechanism for allosteric regulation in protein kinases.