Apo calmodulin binding to the L-type voltage-gated calcium channel Cav1.2 IQ peptide
Apo calmodulin binding to the L-type voltage-gated calcium channel Cav1.2 IQ peptide
复制标题
DOI：
10.1016/j.bbrc.2006.12.070
复制
发表时间：
2007-02-16
影响因子：
3.1
通讯作者：
Kitmitto, Ashraf
中科院分区：
文献类型：
--
作者：
Lian, Lu-Yun;Myatt, Daniel;Kitmitto, Ashraf
钙离子通过L型电压门控钙通道(LTCCs)的内流是钙诱导肌浆网钙释放的触发过程，是心肌收缩的重要步骤。调节LTCC活性的反馈机制有两种：钙依赖失活(CDI)和钙依赖促进(CDF)，两者都是由钙调素(CaM)结合介导的。位于LTCC Ca-v 1.2亚单位胞质结构域中的IQ结构域(aa 1645-1668)与钙负载(Ca+CaM)和无钙CaM(ApoCaM)结合。在这里，我们用核磁共振为apoCaM与IQ肽相互作用的结构基础提供了新的数据，揭示了apoCaM Globe残基在复合体形成时受到最显著的扰动。此外，我们还对纯化的LTCC络合物进行了透射电子显微镜观察，结果表明apoCaM和Ca~(2+)-CaM都能与完整的通道结合。(C)2006 Elsevier Inc.保留所有权利。
The influx of calcium through the L-type voltage-gated calcium channels (LTCCs) is the trigger for the process of calcium-induced calcium release (CICR) from the sarcoplasmic recticulum, an essential step for cardiac contraction. There are two feedback mechanisms that regulate LTCC activity: calcium-dependent inactivation (CDI) and calcium-dependent facilitation (CDF), both of which are mediated by calmodulin (CaM) binding. The IQ domain (aa 1645-1668) housed within the cytoplasmic domain of the LTCC Ca-v 1.2 subunit has been shown to bind both calcium-loaded (Ca2+CaM) and calcium-free CaM (apoCaM). Here, we provide new data for the structural basis for the interaction of apoCaM with the IQ peptide using NMR, revealing that the apoCaM Globe residues are most significantly perturbed upon complex formation. In addition, we have employed transmission electron microscopy of purified LTCC complexes which shows that both apoCaM and Ca2+CaM can bind to the intact channel. (c) 2006 Elsevier Inc. All rights reserved.