Structural Insights into the Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII)
Structural Insights into the Regulation of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII)
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Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）的结构调控
DOI：
10.1101/cshperspect.a035147
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发表时间：
2020-06-01
影响因子：
7.2
通讯作者：
Kuriyan, John
中科院分区：
文献类型：
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作者：
Bhattacharyya, Moitrayee;Karandur, Deepti;Kuriyan, John
Ca 2 +/钙调蛋白依赖性蛋白激酶II（CaMKII）是一种高度保守的丝氨酸/苏氨酸激酶，其在整个人体中普遍表达。CaMKII的特殊亚型在神经元和心脏信号传导中起关键作用。CaMKII独特的全酶结构，具有12-14个激酶结构域，通过灵活的接头连接到中央枢纽，对结构表征提出了巨大的挑战。然而，在确定CaMKII功能的结构机制方面的进展来自于分别研究激酶结构域和枢纽，以及最近对完整全酶的电子显微镜研究。在这篇综述中，我们讨论了我们目前对CaMKII结构的理解。我们还讨论了有趣的发现，CaMKII全酶可以进行激活触发的亚基交换，一个过程，有影响的增强和永久化的CaMKII活性。
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a highly conserved serine/threoni ne kinase that is ubiquitously expressed throughout the human body. Specialized isoforms of CaMKII play key roles in neuronal and cardiac signaling. The distinctive holoenzyme architecture of CaMKII, with 12-14 kinase domains attached by flexible linkers to a central hub, poses formidable challenges for structural characterization. Nevertheless, progress in determining the structural mechanisms underlying CaMKII functions has come from studying the kinase domain and the hub separately, as well as from a recent electron microscopic investigation of the intact holoenzyme. In this review, we discuss our current understanding of the structure of CaMKII. We also discuss the intriguing finding that the CaMKII holoenzyme can undergo activation-triggered subunit exchange, a process that has implications for the potentiation and perpetuation of CaMKII activity.