School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
J Biochem. 2011 Apr;149(4):463-74. doi: 10.1093/jb/mvr006. Epub 2011 Jan 21.
Calmodulin (CaM), a Ca(2+)-binding protein, is a well-known regulator of various cellular functions. One of the targets of CaM is metabotropic glutamate receptor 7 (mGluR7), which serves as a low-pass filter for glutamate in the pre-synaptic terminal to regulate neurotransmission. Surface plasmon resonance (SPR), circular dichroism (CD) spectroscopy and nuclear magnetic spectroscopy (NMR) were performed to study the structure of the peptides corresponding to the CaM-binding domain of mGluR7 and their interaction with CaM. Unlike well-known CaM-binding peptides, mGluR7 has a random coil structure even in the presence of trifluoroethanol. Moreover, NMR data suggested that the complex between Ca(2+)/CaM and the mGluR7 peptide has multiple conformations. The mGluR7 peptide has been found to interact with CaM even in the absence of Ca(2+), and the binding is directed toward the C-domain of apo-CaM rather than the N-domain. We propose a possible mechanism for the activation of mGluR7 by CaM. A pre-binding occurs between apo-CaM and mGluR7 in the resting state of cells. Then, the Ca(2+)/CaM-mGluR7 complex is formed once Ca(2+) influx occurs. The weak interaction at lower Ca(2+) concentrations is likely to bind CaM to mGluR7 for the fast complex formation in response to the elevation of Ca(2+) concentration.
钙调蛋白（CaM）是一种 Ca(2+)-结合蛋白，是各种细胞功能的已知调节剂。CaM 的一个靶标是代谢型谷氨酸受体 7（mGluR7），它作为前突触末端谷氨酸的低通滤波器，调节神经递质传递。采用表面等离子体共振（SPR）、圆二色性（CD）光谱和核磁共振光谱（NMR）研究了与 mGluR7 的 CaM 结合域相对应的肽的结构及其与 CaM 的相互作用。与众所周知的 CaM 结合肽不同，mGluR7 即使在三氟乙醇存在下也具有无规卷曲结构。此外，NMR 数据表明，Ca(2+)/CaM 与 mGluR7 肽的复合物具有多种构象。已经发现 mGluR7 肽即使在没有 Ca(2+)的情况下也与 CaM 相互作用，并且结合是针对无 Ca(2+) apo-CaM 的 C 结构域而不是 N 结构域。我们提出了 CaM 激活 mGluR7 的可能机制。在细胞的静止状态下，apo-CaM 与 mGluR7 之间发生预结合。然后，一旦发生 Ca(2+)内流，就会形成 Ca(2+)/CaM-mGluR7 复合物。在较低 Ca(2+)浓度下的弱相互作用可能会将 CaM 结合到 mGluR7 上，以快速形成复合物，以响应 Ca(2+)浓度的升高。
