DYNAMIC EVENTS IN MYOSIN DURING CONTRACTION OF MUSCLE

肌肉收缩期间肌球蛋白的动态事件

• 批准号: 3155229
• 负责人: EMIL REISLER
• 金额: $ 27.93万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3155229
• 关键词: acidity /alkalinity; actins; adenosine triphosphate; adenosinetriphosphatase; bioenergetics; caldesmon; chemical binding; conformation; crosslink; electron microscopy; fluorescence spectrometry; fluorescent dye /probe; immunocytochemistry; ionic strengths; laboratory rabbit; light scattering; molecular site; muscle contraction; myofibrils; myosins; phosphorylation; polymerization; protein engineering; protein structure function; tropomyosin; troponin

The long term objective of the proposed research is to elucidate the structural and chemical basis of muscle contraction. This objective will be pursued by working on three related research projects aimed at the clarification of: (1) the regulation of muscle contraction; (2) function-structure relationships on actin, myosin, and actomyosin interface; and (3) the assembly of myofibrilar structures. (1)The specific aims of the regulation project are: (i) to test the hypothesis that the N-terminal segment of actin is involved in the regulation of contraction in different muscles; (ii) to clarify the interaction of caldesmon with actin; and (iii) to test under physiological conditions the steric block and catalytic mechanisms for regulation of muscle contraction. (2)The goals of the studies on actin, myosin, and actomyosin interface are: (i) to clarify the role of selected sites on actin and myosin in the strong (-ATP) and weak (+ATP) actomyosin binding; and (ii) to determine the role of the SHI peptide, selected sites on actin and myosin, and dynamic motions in actin in the contractile process. The first two projects will involve immunochemical, enzymological, chemical modification, in vitro motility, fluorescence and sedimentation experiments with peptide antibodies, modified and unmodified proteins, actin mutants, myosin and actin filaments, myofibrils, and muscle fibers. (3)The specific aims of the assembly project are: (i) to clarify the role of regulatory factors in the nucleation, growth, and stability of myosin filaments; (ii) to characterize solution properties of titin; and (iii) to examine the formation of myosin filaments in myofibrils by using myosin from skeletal muscle hybridized with light chain-2 from smooth muscle myosin. These studies will employ hydrodynamic, light scattering, electron microscopy, and spectroscopic techniques. The research proposed in this application will result in an improved understanding of contractile processes in muscle and non-muscle cells.

拟议研究的长期目标是阐明 肌肉收缩的结构和化学基础。 这一目标将 开展三个相关的研究项目， 澄清：（1）肌肉收缩的调节;（2） 肌动蛋白、肌球蛋白和肌动球蛋白的功能-结构关系 界面;（3）肌原纤维结构的组装。 （1）该管制项目的具体目标是： 假设肌动蛋白的N-末端片段参与了 调节不同肌肉的收缩;（ii）澄清 钙调素与肌动蛋白的相互作用;以及（iii）在 生理条件下的空间位阻和催化机制 调节肌肉收缩。 （2）肌动蛋白、肌球蛋白和肌动球蛋白的研究目标 接口是：（i）阐明肌动蛋白上选定位点的作用， 强（-ATP）和弱（+ATP）肌动球蛋白结合中的肌球蛋白;和（ii） 为了确定SHI肽的作用，选择肌动蛋白上的位点， 肌球蛋白和肌动蛋白在收缩过程中的动态运动。 前两个项目将涉及免疫化学，酶学， 化学修饰、体外运动、荧光和沉降 用肽抗体，修饰和未修饰的蛋白质， 肌动蛋白突变体、肌球蛋白和肌动蛋白丝、肌原纤维和肌纤维。 （3）大会项目的具体目标是：（一）澄清 调节因子在成核、生长和稳定中的作用 （ii）表征肌联蛋白的溶液性质;和 (iii)通过使用，检查肌原纤维中肌球蛋白丝的形成。 来自骨骼肌的肌球蛋白与来自平滑肌的轻链2杂交 肌球蛋白 这些研究将采用流体力学，光散射， 电子显微镜和光谱技术。 本申请中提出的研究将导致改进的 了解肌肉和非肌肉细胞的收缩过程。