COOPERATIVE EFFECTS OF SMOOTH MUSCLE REGULATION

平滑肌调节的协同作用

• 批准号: 6268383
• 负责人: SHERWIN LEHRER
• 金额: $ 20.12万
• 依托单位: BOSTON BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6268383
• 关键词: actins; adenosinetriphosphatase; animal tissue; caldesmon; chemical binding; chemical kinetics; conformation; enzyme activity; microfilaments; muscle contraction; myosins; phosphorylation; protein sequence; protein structure function; smooth muscle; striated muscles; tropomyosin; ultracentrifugation

The broad long-term objective of this project is to understand the couple interactions among the smooth muscle thin filament protein components, actin, tropomyosin, caldesmon and myosin that are involved in the cooperative activation and relaxation processes of smooth muscle contraction. Specifically, we aim to: 1) understand the difference between the activating properties of smooth muscle compared to striated muscle tropomyosin in terms of the end-to-end interactions between tropomyosins along the thin filament; 2) determine the steps in the actomyosin ATPase cycle that are affected by phosphorylation; 3) explain the "latch" state of smooth muscle, whereby the muscle can maintain force over long times without much ATP usage at low degrees of phosphorylation; 4) Determine if caldesmon functions in smooth muscle in an analogous manner to troponin in striated muscle and explore the role of other components in the regulation process. The methods to be used include ATPase activity measurements, kinetics and equilibrium titrations with fluorescence probes on the protein components. Tropomyosin isoforms isolated from smooth muscle and mutated tropomyosins will be used. With the information obtained from these studies the basic mechanisms of smooth muscle regulation will be better understood so that the several smooth muscle abnormalities can be characterized.

这个项目的长期目标是了解这对夫妇 平滑肌细丝蛋白组分之间的相互作用， 肌动蛋白，原肌球蛋白，钙调蛋白和肌球蛋白参与了 平滑肌的协同激活和松弛过程 收缩。具体来说，我们的目标是：1）了解之间的区别 平滑肌与横纹肌相比， 原肌球蛋白之间的端对端相互作用 沿着细丝; 2）确定肌动球蛋白ATP酶的步骤 3）解释“闩锁”状态 平滑肌，从而肌肉可以保持力量很长一段时间 在低磷酸化程度下没有太多ATP使用; 4）确定是否 钙调蛋白在平滑肌中的功能类似于肌钙蛋白， 横纹肌，并探讨其他成分的调节作用 过程使用的方法包括ATP酶活性测量， 动力学和平衡滴定与荧光探针上的 蛋白质成分分离自平滑肌的原肌球蛋白同种型， 将使用突变的原肌球蛋白。从以下来源获得的信息 这些研究将平滑肌调节的基本机制 更好地理解，以便可以 表征了