结构洞察钙/钙调蛋白依赖性蛋白激酶 II（CaMKII）的调节。
Structural Insights into the Regulation of Ca/Calmodulin-Dependent Protein Kinase II (CaMKII).
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, California 94720.
出版信息
Cold Spring Harb Perspect Biol. 2020 Jun 1;12(6):a035147. doi: 10.1101/cshperspect.a035147.
Abstract
Ca/calmodulin-dependent protein kinase II (CaMKII) is a highly conserved serine/threonine 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.
摘要
钙/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，在人体全身广泛表达。CaMKII 的特殊同工型在神经元和心脏信号转导中发挥关键作用。CaMKII 的独特全酶结构，由 12-14 个激酶结构域通过柔性接头连接到中央枢纽上，给结构特征鉴定带来了巨大的挑战。尽管如此，通过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，在确定 CaMKII 功能的结构机制方面已经取得了进展。在这篇综述中，我们讨论了我们对 CaMKII 结构的现有理解。我们还讨论了一个有趣的发现，即 CaMKII 全酶可以发生激活触发的亚基交换，这一过程对 CaMKII 活性的增强和持续具有重要意义。
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