Yin Chang-Cheng, Blayney Lynda M, Lai F Anthony
Department of Biophysics, Peking University Health Science Center, Peking University, 38 Xueyuan Road, Beijing 100083, China.
J Mol Biol. 2005 Jun 10;349(3):538-46. doi: 10.1016/j.jmb.2005.04.002. Epub 2005 Apr 25.
Ryanodine receptor-calcium release channels play a pivotal role in the calcium signaling that mediates muscle excitation-contraction coupling. Their membrane organization into regular patterns, functional gating studies and theoretical analysis of receptor clustering have led to models that invoke allosteric interaction between individual channel oligomers as a critical mechanism for control of calcium release. Here we show that in reconstituted "checkerboard-like" lattices that mimic in situ membrane channel arrays, each oligomer is interlocked physically with four adjacent oligomers via a specific domain-domain interaction. Direct physical coupling between ryanodine receptors provides structural evidence for an inter-oligomer allosteric mechanism in channel regulation. Therefore, in addition to established cytosolic and luminal regulation of function, these observations indicate that channel-channel communication through physical coupling provides a novel mode of regulation of intracellular calcium release channels.
兰尼碱受体 - 钙释放通道在介导肌肉兴奋 - 收缩偶联的钙信号传导中起关键作用。它们在膜上形成规则模式的组织、功能门控研究以及受体聚集的理论分析，已产生了一些模型，这些模型认为单个通道寡聚体之间的变构相互作用是控制钙释放的关键机制。在这里，我们表明，在模拟原位膜通道阵列的重构“棋盘状”晶格中，每个寡聚体通过特定的结构域 - 结构域相互作用与四个相邻的寡聚体物理互锁。兰尼碱受体之间的直接物理偶联为通道调节中的寡聚体间变构机制提供了结构证据。因此，除了已确定的功能的胞质和管腔调节外，这些观察结果表明，通过物理偶联的通道 - 通道通讯提供了一种调节细胞内钙释放通道的新模式。
