Department of Physiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 26-28, Nijmegen, 6525, GA, The Netherlands.
Pflugers Arch. 2013 Nov;465(11):1507-19. doi: 10.1007/s00424-013-1278-0. Epub 2013 Apr 23.
The Ca²⁺-binding protein calmodulin (CaM) is a well-known regulator of ion-channel activity. Consequently, the Protein Data Bank contains many structures of CaM in complex with different fragments of ion channels that together display a variety of binding modes. In addition to the canonical interaction, in which CaM engages its target with both its domains, many of the ion-channel-CaM complexes demonstrate alternative non-canonical binding modes that depend on the target and experimental conditions. Based on these findings, several mechanisms of ion-channel regulation by CaM have been proposed, all exploiting its plasticity and flexibility in interacting with its targets. In this review, we focus on complexes of CaM with either the voltage-gated calcium channels; the voltage-gated sodium channels or the small conductance calcium-activated potassium channels, for which both structural and functional data are available. For each channel, the functional relevance of these structural data and possible mechanism of calcium-dependent (in)activation and/or facilitation are discussed in detail.
钙结合蛋白钙调蛋白（CaM）是一种众所周知的离子通道活性调节剂。因此，蛋白质数据库中包含许多与不同离子通道片段结合的 CaM 结构，这些结构共同显示出多种结合模式。除了 CaM 用其两个结构域与靶标结合的经典相互作用外，许多离子通道-CaM 复合物表现出依赖于靶标和实验条件的替代非经典结合模式。基于这些发现，已经提出了 CaM 调节离子通道的几种机制，所有这些机制都利用了 CaM 与其靶标相互作用的可塑性和灵活性。在这篇综述中，我们重点介绍 CaM 与电压门控钙通道、电压门控钠通道或小电导钙激活钾通道的复合物，这些通道都有结构和功能数据。对于每种通道，我们详细讨论了这些结构数据的功能相关性以及钙依赖性（失活和/或激活）和/或易化的可能机制。
