Integration of signaling in the kinome: Architecture and regulation of the αC Helix.
Integration of signaling in the kinome: Architecture and regulation of the αC Helix.
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激酶组中信号传导的整合：αC 螺旋的结构和调节。
DOI：
10.1016/j.bbapap.2015.04.007
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kornev,AlexandrP
中科院分区：
文献类型：
--
作者：
Taylor,SusanS;Shaw,AndreyS;Kannan,Natarajan;Kornev,AlexandrP
真核生物蛋白激酶已经进化为高度调控和动态的分子开关，通常保持在非激活状态，然后对细胞外信号做出反应而激活。活性激酶的标志性特征是一种被称为调节性(R)脊椎的疏水脊椎，它由四个残基组成，两个在N叶，两个在C叶。RS1在催化环中，RS2是DFG基序中的Phe，Rs3在αC-螺旋的C末端，Rs4在β4的开始。R-脊柱的组装通常通过激活环的磷酸化来促进。组装的R-脊柱汇集了将磷酸盐从ATP转移到系留蛋白底物所必需的所有功能基序。这包括锚定三磷酸腺苷的G-环、催化环、与激活环融合的DFG基序和αC-螺旋。我们在这里集中讨论αC-螺旋的性质，展示1)残基如何与分子的不同部分通信，2)它如何作为R-脊柱组装的结果被招募到活性部位，以及3)它是如何被位于保守的激酶核心之外的连接物/基序/蛋白质调节的。本文是一期特刊的一部分，题为：蛋白激酶的抑制物。
Eukaryotic protein kinases have evolved to be highly regulated and dynamic molecular switches that are typically kept in an inactive state and then activated in response to extracellular signals. The hallmark signature of an active kinase is a hydrophobic spine called the regulatory (R) spine, which consists of four residues, two in the N-lobe and two in the C-lobe. RS1 is in the catalytic loop, RS2 is the Phe in the DFG motif, RS3 is at the C-terminus of the αC-Helix, and RS4 is at the beginning of β4. Assembly of the R-spine is typically facilitated by phosphorylation of the Activation Loop. The assembled R-spine brings together all of the functional motifs that are essential for transferring the phosphate from ATP to a tethered protein substrate. This includes the G-Loop, which anchors the ATP, the catalytic loop, the DFG motif fused to the Activation Loop, and the αC-Helix. We focus here on the properties of the αC-Helix showing 1) how residues communicate with different parts of the molecule, 2) how it is recruited to the active site as a consequence of assembling of the R-spine, and 3) how it is regulated by linkers/motifs/proteins that lie outside the conserved kinase core. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.