STRUCTURAL CHANGES AND SIGNALLING IN CALCIUM REGULATORS

目的是了解钙的结构基础 调节细胞过程。 建议研究 不同功能钙调节蛋白的结构 状态，主要使用小角度解决方案散射和 光谱技术如傅里叶变换红外 光谱（FTIR）和圆二色性（CD）。 具体地说， 工作将集中在类结构相关，虽然 功能多样的调节蛋白，包括钙调蛋白， 肌钙蛋白C和小清蛋白。 初步研究表明， 溶液环境对钙调素的影响 肌钙蛋白C结构。 今后的工作将更多地针对 这些蛋白质与它们体内其他成分的相互作用 生化系统 我们尤其希望： o进一步研究溶液环境对 肌钙蛋白C和钙调蛋白的结构; o研究结构和功能的后果， 钙调蛋白的共价修饰; o研究外源性和内源性钙调素与 磷酸化酶激酶亚基; o研究钙调素与钙调素之间的相互作用， 肌球蛋白轻链激酶和相关肽的结合结构域。 小角溶液散射将用于表征 这些系统的组件的整体形状和相互作用， 不同的激活状态。 FTIR和CD光谱将 用于评估二级结构含量，特别是， 为了监测伴随着这些变化的二级结构的变化， 功能状态的变化。 低分辨率的解释 使用这些技术获得的结构信息将 高分辨率的可用性大大增强 蛋白质的晶体学数据。 长期的目标是了解分子机制， 钙调节

The objective is to understand the structural basis for calcium regulation in cellular processes. It is proposed to study the structures of calcium regulating proteins in different functional states, principally using small angle solution scattering and spectroscopic techniques such as Fourier transform infra-red spectroscopy (FTIR) and circular dichroism (CD). Specifically, the work will focus on the class of structurally related, though functionally diverse, regulatory proteins that includes calmodulin, troponin C and parvalbumin. Initial studies have concerned the effects of the solution environment on the calmodulin and troponin C structures. Future work will be directed more toward the interactions of these proteins with other components in their biochemical systems. In particular, we wish to: o further study the influence of the solution environment on the structures of troponin C and calmodulin; o investigate the structural and functional consequences of covalent modifications of calmodulin; o study the interactions of extrinsic and intrinsic calmodulin with the subunits of phosphorylase kinase; o study the interactions of calmodulin with the calmodulin binding domain of myosin light chain kinase and related peptides. Small angle solution scattering will be used to characterize the overall shapes and interactions of components of these systems in different states of activation. FTIR and CD spectroscopy will be used to evaluate secondary structure content, and, in particular, to monitor changes in secondary structure that accompany changes in functional state. Interpretation of the low resolution structural information that is obtained using these techniques will be greatly enhanced by the availability of high resolution crystallographic data on the proteins. The long term goal is to understand the molecular mechanism for calcium regulation.