Molecular Movements in Bioenergy Transduction

该申请提出了一项国际合作， 三个美国和三个苏联实验室 科学 目的是确定肌球蛋白之间的相对运动 亚片段1（S-1）和肌动蛋白（复合物）的影响下， ATP水解的过程 这些运动， 肌肉收缩和一些细胞运动，被认为是 完成能量转换（ATP水解的自由能 机械（力x距离）功）。 光学检测 分子探针将成对使用， 相关重定向或检测标量的变化 距离，目的是决定运动是否 在转导中，S-1的全局旋转是由非常 较小的内部位移（目前的“标准模式”）或 内部运动是否包括大部分S-1（如 域间移动）。 将努力-利用 差示扫描量热法圆二色性 获得域结构的指示，并检查 交叉连接对这些假定运动的影响 域. 还将尝试发展两种物理 (S-1定向纯F-肌动蛋白）和分子图形模型， 为了简化上述研究。 除了六 高级调查员，几个学生和年轻的同事 将参与这项工作。 的主要意义 这个建议是基本的。 由于没有生物能量转换器 还没有被解释过，发现设计的可能性 特征也可能具有实际意义。

This application proposes an international cooperation among three American and three Soviet laboratories. The scientific objective is to define the relative movements between myosin subfragment 1 (S-1) and actin (in complex) under the influence of ATP hydrolysis going on in S-1. These movements, underlying muscle contraction and some cell motility, are thought to accomplish energy transduction (free energy of ATP hydrolysis to mechanical (force x distance) work). Optically-detected molecular probes are to be used in pairs, either to detect correlated re-orientation or to detect change in scalar distances, the purpose being to decide whether the movements in transduction are a global rotation of S-1 caused by very small internal displacements (present "standard model") or whether internal movements encompass most of S-1 (as in interdomain movement). Efforts will be made---using differential scanning calorimetry circular dichroism---to obtain indications of domain structure, and also to examine the effect of crosslinks on the putative movements of these domains. Attempts also will be made to develop both physical (S-1 on oriented pure F-actin) and molecular graphic models in order to simplify the foregoing studies. Besides the six senior investigators, several students and young associates would participate in this work. The principal significance of this proposal is basic. Since no biological energy transducer has yet been explained, the possibility of discovering design features also may be of practical interest.