REGULATION OF CARDIAC AND SKELETAL MUSCLE CONTRACTION

肌钙蛋白和原肌球蛋白调节血管紧张素转换酶的分子机制 肌动蛋白和肌球蛋白在骨骼肌中的相互作用将被研究， 包括对结构变化和相互作用的详细研究 在肌钙蛋白亚基和其他细丝蛋白中，肌动蛋白和 原肌球蛋白。这将通过研究a)详细的 TnC、TnI和TnT之间亚基间结合的强度和位置；b) 金属诱导的结构信息向蛋白质形成的转移 肌动蛋白-肌球蛋白相互作用对TNC的影响 钙离子与肌钙蛋白结合的协同性。主要实验工具 因为这些研究将是光学和磁光谱学以及 氢/氚交换研究。预计这项研究将提交 这一建议可能有助于理解监管 肌肉中的过程。在这里开发了关于金属-蛋白质和 蛋白质之间的相互作用在一般情况下应该是重要的 因为相似的过程广泛分布在 生物系统中的各种生理过程。最后， 关于正常肌肉功能的知识对于最终的 对疾病过程中潜在分子机制的理解 肌肉。

The molecular mechanisms by which troponin and tropomyosin regulate the interaction of actin and myosin in skeletal muscle will be investigated, involving a detailed study of the changes in structure and interactions among the troponin subunits and the other thin filament proteins, actin and tropomyosin. This will be approached by studying a) details of the strength and sites of intersubunit binding between TnC, TnI and TnT; b) the transfer of metal-induced structural information to proteins forming complexes with TnC; c) the effects of actin-myosin interactions on the cooperativity of Ca2+ binding to troponin. The major experimental tools for these studies will be optical and magnetic spectroscopy and hydrogen/tritium exchange studies. It is expected that the study presented in this proposal may contribute to an understanding of the regulatory processes in muscles. New knowledge developed here on metal-protein and protein-protein interactions should be of significance in the general fied of protein chemistry since similar processes are widely distributed among biological systems in a variety of physiological processes. Finally, knowledge about normal muscle function is essential for the eventual understanding of the molecular mechanisms underlying disease processes in muscle.