BIOPHYSICAL CHEMICAL STUDIES OF MUSCLE PROTEINS

肌肉蛋白的生物物理化学研究

• 批准号: 3481354
• 负责人: William J Harrington
• 金额: $ 40.43万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-09-01 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3481354
• 关键词: antibody; biomechanics; conformation; crosslink; electron microscopy; immunochemistry; immunoglobulin G; molecular rearrangement; muscle contraction; muscle proteins; myofibrils; optical rotation; sarcomeres; striated muscles; temperature jump; thermodynamics

We plan to continue current physico-chemical studies on the molecular mechanism of force-generation in vertebrate skeletal muscle. In these studies, we hope to test the helix-coil model proposed for force-generation in muscle and compare the results with those expected according to the classical rotating cross- bridge mechanism. An infrared, iodine photodissociation laser will be used to heat fibers (approximately 5 degrees C) under 1 mu sec and the coupling between transient melting in (the S-2 region of) rigor cross-bridges and the development of tension will be investigated in detail. Experiments will be carried out under ionic conditions where the S-2 elements of rigor bridges are stabilized by association with the thick filament backbone and where they are released from the backbone at various temperatures and sarcomere lengths. The kinetic constants and amplitudes of the force transients will be compared to those of activated fibers under a variety of environmental conditions in these two states in an attempt to demonstrate the presence or absence of common features which could distinguish between the two mechanisms. We also plan to continue our investigations of cross-linking of the rod segments within the thick filament core of glycerinated rigor fibers in an attempt to decouple force generation in the S-2 and S-1 regions of the cross-bridges. The effect of polyclonal antibodies specific to the S-2 region of myosin on contractile force in glycerinated fibers is also under study. These experiments, like the cross-linking studies, are designed to determine whether modulation of S-2 binding of a cycling bridge to the thick filament surface has a direct effect on force-generation. The long range goal of these studies is to understand the process of muscle contraction at a fundamental level. An understanding of this process has wide-ranging medical implications.

我们计划继续目前的物理化学研究 脊椎动物骨骼力产生的分子机制 肌肉。 在这些研究中，我们希望测试螺旋线圈模型 建议用于肌肉产生力并比较结果 与根据经典旋转交叉预期的那些 桥梁机制。 红外碘光解激光 将用于将纤维加热（约 5 摄氏度）低于 1 微秒和瞬态熔化之间的耦合（S-2 的地区）严格的跨桥和紧张局势的发展将 进行详细调查。 实验将在 离子条件，其中严格桥的 S-2 元素为 通过与粗丝主链结合而稳定， 他们在不同的地方从骨干中释放出来 温度和肌节长度。 动力学常数和 力瞬变的幅度将与 各种环境条件下的活性纤维 这两个国家试图证明存在或 缺乏可以区分的共同特征 两种机制。 我们还计划继续调查 粗丝内棒段的交联 甘油刚性纤维的核心，试图解耦力 跨桥 S-2 和 S-1 区域的发电。 这 S-2区特异性多克隆抗体的作用 肌球蛋白对甘油纤维收缩力的影响也正在研究中 学习。 这些实验，如交联研究， 旨在确定是否调节 S-2 结合 骑行桥对粗丝表面有直接影响 关于力的产生。 这些研究的长期目标是 从根本上了解肌肉收缩的过程 等级。 对这一过程的理解具有广泛的医学意义 影响。