REGULATION IN STRIATED, SMOOTH, AND CARDIAC MUSCLES

横纹肌、平滑肌和心肌的调节

基本信息

批准号：
3150983
负责人：
ANDREW G SZENT-GYORGYI
金额：
$ 22.2万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1977
资助国家：
美国
起止时间：
1977-05-01 至 1987-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3150983
关键词：
X ray crystallography biological information processing crosslink electron microscopy immunochemistry muscle contraction myocardium myofibrils phosphorylation radiotracer saltwater environment smooth muscle species difference striated muscles

项目摘要

Regulation of muscle contraction by the thick filaments will be studied at the molecular level. Two control system are known in muscle. In thin filament regulation availability of sites on actin is altered by troponin-tropomyosin, in thick filament regulation sies on myosin are modified by the regulatory light chains. Both systems operate by preventing interactions between actin and myosin in the absence of calcium. Control is exerted by the thin in vertebrate straited muscles, by the thick filaments in molluscan muscles; both regulatory mechanisms operate in many invertebrate muscles. Scallop myosin is particularly useful for the study of subunit regulation since the rgulatory light chains can be fully dissociated from the heavy chains without denaturing the molecule. The regulatory light chains are not needed for contraction, in their absence, however, myosin is no longer regulated. The light chaings can be quantitatively recombined with scallop myosin, and regulation is totally regained. We plan to define the role of the other myosin subunits, the essential light chains in regulation. A regulatory role of the essential light chains is indicated since antibodies specific against this subunit selectively interfere with regulation. We will attempt to remove the essential light chains from myosin with the aid of chaeotropic agents, or exchange these with light chains of non-regulated myosins. We will try to determine interactions and overlap between regulatory and essential light chains by using photosensitive cross-linkers attached to regulatory light chains at known positions. We plan to estimate distance between the two light chain types, and between these light chains and havey chains in the presence and the absence of calcium, ATO and actin by the specific labeling with suitable donor-acceptor pairs. Heavy metal labeled regulatory light cahins will be used as markers to analyse the myosin molecules and the myosin fialments in fiber bundles. We plan to extend the selective labeling techniques of light chain and heavy chains to myofibrils and fiber bundles suitable for X-ray diffraction and tension studies in attempting to develop a preparation that may help to relate chemical and mechanical events.

将研究厚细丝的肌肉收缩调节分子水平。肌肉中已知两个控制系统。瘦肌动蛋白上位点的细丝调节可用性被改变在肌球蛋白上，肌钙蛋白 - 肌球蛋白在较厚的细丝调节中是通过调节灯链修饰。两个系统均通过在没有的情况下防止肌动蛋白与肌球蛋白之间的相互作用钙。控制由薄薄的脊椎动物海峡肌肉施加软体动物肌肉中的厚细丝；两种调节机制在许多无脊椎动物肌肉中运动。扇贝肌球蛋白特别是由于rgulation Light链，可用于研究亚基调节可以完全与重链完全解离，而无需贬低分子。收缩不需要调节轻链但是，它们的缺失不再受到调节。轻木丝可以定量地与扇贝肌球蛋白重新组合，调节为完全恢复。我们计划定义其他肌球蛋白亚基的作用，调节中的基本光链。监管角色指示基本的轻链，因为针对此的抗体特定于此亚基选择性干扰调节。我们将尝试删除肌球蛋白的基本光链借助卫生剂，或用未调节的肌球蛋白的轻链交换。我们将尝试确定调节和基本之间的相互作用和重叠通过使用与调节的光敏交联链通过光敏链已知位置的轻链。我们计划估计两种轻型链类型，这些轻链和链条之间特异性的存在和不存在钙，ATO和肌动蛋白用合适的供体对配对进行标记。重金属标记调节灯卡金斯将用作分析肌球蛋白的标记纤维束中的分子和肌球蛋白叶。我们计划扩展轻链和重链的选择性标签技术到肌原纤维和适合X射线衍射和张力研究的纤维束试图制定可能有助于关联化学和机械事件。

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Proximity of regulatory light chains in scallop myosin.

扇贝肌球蛋白中调节轻链的邻近性。

DOI：
10.1016/0022-2836(85)90213-x
发表时间：
1985
期刊：
Journal of molecular biology
影响因子：
5.6
作者：
Hardwicke,PM;Szent-Györgyi,AG
通讯作者：
Szent-Györgyi,AG

SH-1 modification of rabbit myosin interferes with calcium regulation.

兔肌球蛋白的 SH-1 修饰干扰钙调节。

DOI：
10.1007/bf01739854
发表时间：
1989
期刊：
Journal of muscle research and cell motility
影响因子：
2.7
作者：
Titus,MA;Ashiba,G;Szent-Györgyi,AG
通讯作者：
Szent-Györgyi,AG

Amino acid sequence of myosin essential light chain from the scallop Aquipecten irradians.

DOI：
10.1021/bi00371a056
发表时间：
1986-11
期刊：
Biochemistry
影响因子：
2.9
作者：
John H. Collins;J. Kendrick-Jones;Ross Jakes;John Leszyk;Winifred Barouch;J. Theibert;Judith Spiegel;Andrew G. Szent-Gyorgyi
通讯作者：
John H. Collins;J. Kendrick-Jones;Ross Jakes;John Leszyk;Winifred Barouch;J. Theibert;Judith Spiegel;Andrew G. Szent-Gyorgyi

Hybrid formation between scallop myofibrils and foreign regulatory light-chains.

扇贝肌原纤维和外来调节轻链之间的杂交形成。