STRUCTURAL CHANGES AND SIGNALLING IN CALCIUM REGULATORS

目的是了解钙的结构基础。 细胞过程中的调节。建议研究一下 不同功能钙调节蛋白的结构 态，主要使用小角度溶液散射和 傅里叶变换红外等光谱技术 红外光谱(FTIR)和圆二色谱(CD)。具体来说， 不过，这项工作将集中在结构上相关的类别 功能多样的调节蛋白，包括钙调蛋白， 肌钙蛋白C和小白蛋白。初步研究关注到 溶液环境对钙调素和钙调素的影响 肌钙蛋白C结构。今后的工作将更多地向 这些蛋白质与其体内其他成分的相互作用 生化系统。我们特别希望： O进一步研究溶液环境对环境的影响 肌钙蛋白C和钙调蛋白的结构； O调查以下项目的结构和功能后果 钙调蛋白的共价修饰； 研究外源性和内源性钙调蛋白与 磷酸化酶激酶的亚基； 研究钙调蛋白与钙调蛋白的相互作用 肌球蛋白轻链激酶及其相关多肽的结合域。 小角溶液散射将被用来表征 中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光谱将是 用于评估二级结构内容，尤其是， 监视随之而来的二级结构变化 功能状态的变化。对低分辨率的解释 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了 蛋白质的结晶学数据。 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.