Han Hong-mei, Wei Ri-sheng, Lai F Anthony, Yin Chang-cheng
Department of Biophysics, Peking University Health Science Centre, Peking University, Beijing 100083, China.
Acta Pharmacol Sin. 2006 Jul;27(7):888-94. doi: 10.1111/j.1745-7254.2006.00386.x.
To elucidate the molecular nature of sulfhydryl modification by hydrogen peroxide on type 1 ryanodine receptor (RyR1).
Rabbit skeletal muscle sarcoplasmic reticulum was treated with hydrogen peroxide, then RyR1 complex was isolated. The proteins in the complex were analysed by electrophoresis, Western blot and electron microscopy.
(1) Hydrogen peroxide induces inter-subunit cross-linking within the tetrameric RyR1 molecule; (2) in parallel to inter-subunit cross-linking, the RyR1 molecule changes morphology; (3) the chemical and morphological changes are reversible: upon reduction by reducing agents, the RyR1 molecule regains its original state.
These findings suggest that the molecular mechanism of RyR1 channel activity in sarcoplasmic reticulum regulated by hydrogen peroxide is through inter-subunit cross-linking within the tetrameric RyR1 molecule, which in turn induces structural changes of RyR1.
阐明过氧化氢对1型兰尼碱受体（RyR1）巯基修饰的分子本质。
用过氧化氢处理兔骨骼肌肌浆网，然后分离RyR1复合物。通过电泳、蛋白质印迹和电子显微镜分析复合物中的蛋白质。
（1）过氧化氢诱导四聚体RyR1分子内亚基间交联；（2）与亚基间交联同时，RyR1分子形态发生改变；（3）化学和形态学变化是可逆的：经还原剂还原后，RyR1分子恢复其原始状态。
这些发现表明，过氧化氢调节肌浆网中RyR1通道活性的分子机制是通过四聚体RyR1分子内亚基间交联，进而诱导RyR1的结构变化。
