X-RAY INTERFERENCE STUDIES OF TROPONIN MOVEMENTS DURING MUSCLE ACTIVATION

肌肉激活过程中肌钙蛋白运动的 X 射线干扰研究

• 批准号: 7954907
• 负责人: HUGH HUXLEY
• 金额: $ 1.74万
• 依托单位: ILLINOIS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7954907
• 关键词: Actins; Binding; Biophysics; Calcium Binding; Calcium ion; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Event; Filament; Funding; Goals; Grant; Institution; Measures; Microfilaments; Movement; Muscle; Myosin ATPase; Positioning Attribute; Research; Research Personnel; Resolution; Resources; Roentgen Rays; Side; Site; Skeletal Muscle; Slide; Source; Structure; Suggestion; Time; Tropomyosin; Troponin; United States National Institutes of Health; genetic regulatory protein; nanometer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Vertebrate skeletal muscle is switched on by the action of calcium ions released from storage sites in the muscle. Calcium binds to the regulatory protein troponin, part of a complex in the actin-containing filaments that actively slide past the myosin filaments during contraction.This binding alters the position of the second regulatory protein tropomyosin, which controls access of the myosin crossbridges to the underlying actin filaments, necessary for tension development. It is already well-established that tropomyosin changes its azimuthal position on actin during activation, but how this is brought about is at present unknown. However, the high-resolution crystallographic structure of troponin has been solved recently, and there are suggestions that part of that structure could undergo a tilting movement to move tropomyosin. This might show up as small changes in the axial position of the center of mass of troponin. These could be measured by studying the interference fine structure of the 385A meridional reflections from the axial repeat of troponin along actin filaments. This fine structure is generated by symmetrical positioning of actin filaments on either side of the Z-lines, and changes in such fine structure enable one to measure changes in axial position with sub-nanometer accuracy. The goal is to study this phenomenon in a time-resolved manner, so as to correlate the changes in axial position with other events during activation of muscle.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 脊椎动物的骨骼肌是通过肌肉中储存部位释放的钙离子的作用来启动的。钙离子与调节蛋白肌钙蛋白结合，肌钙蛋白是含肌动蛋白的肌丝中复合物的一部分，在收缩过程中，肌钙蛋白会主动滑过肌球蛋白丝，这种结合改变了第二种调节蛋白原肌球蛋白的位置，原肌球蛋白控制肌球蛋白跨桥进入下面的肌动蛋白丝，这是张力发展所必需的。 已经确定的是，原肌球蛋白在激活过程中改变了它在肌动蛋白上的方位角位置，但这是如何引起的目前还不清楚。然而，肌钙蛋白的高分辨率晶体结构最近已经得到解决，并且有建议认为该结构的一部分可能经历倾斜运动以移动原肌球蛋白。这可能表现为肌钙蛋白质心轴向位置的微小变化。这些可以通过研究肌钙蛋白沿着肌动蛋白丝的轴向重复的385 A构象反射的干涉精细结构来测量。这种精细结构是由Z线两侧的肌动蛋白丝对称定位产生的，这种精细结构的变化使人们能够以亚纳米精度测量轴向位置的变化。我们的目标是以时间分辨的方式研究这种现象，以便将轴向位置的变化与肌肉激活期间的其他事件相关联。