Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA.
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13579-83. doi: 10.1073/pnas.1207606109. Epub 2012 Aug 6.
Calmodulin (CaM) is a ubiquitous intracellular calcium sensor that directly binds to and modulates a wide variety of ion channels. Despite the large repository of high-resolution structures of CaM bound to peptide fragments derived from ion channels, there is no structural information about CaM bound to a fully folded ion channel at the plasma membrane. To determine the location of CaM docked to a functioning KCNQ K(+) channel, we developed an intracellular tethered blocker approach to measure distances between CaM residues and the ion-conducting pathway. Combining these distance restraints with structural bioinformatics, we generated an archetypal quaternary structural model of an ion channel-CaM complex in the open state. These models place CaM close to the cytoplasmic gate, where it is well positioned to modulate channel function.
钙调蛋白（CaM）是一种普遍存在的细胞内钙传感器，可直接结合并调节多种离子通道。尽管有大量高分辨率的 CaM 与来自离子通道的肽片段结合的结构信息，但在质膜处，没有关于与完全折叠的离子通道结合的 CaM 的结构信息。为了确定与功能齐全的 KCNQ K(+) 通道结合的 CaM 的位置，我们开发了一种细胞内束缚阻断剂方法来测量 CaM 残基与离子传导途径之间的距离。将这些距离约束与结构生物信息学相结合，我们生成了一个开放状态下的离子通道-CaM 复合物的典型四级结构模型。这些模型将 CaM 置于接近细胞质门的位置，使其能够很好地调节通道功能。
