Molecular Movements in Bioenergy Transduction

这项申请提出了三个美国实验室和三个苏联实验室之间的国际合作。科学目的是确定肌球蛋白亚片段1(S-1)和肌动蛋白(复合体)在S-1中进行的三磷酸腺苷水解影响下的相对运动。这些运动，潜在的肌肉收缩和一些细胞运动，被认为完成了能量传递(ATP水解到机械功(力x距离)的自由能)。光学检测的分子探针将成对使用，要么检测相关的重新定向，要么检测标量距离的变化，目的是确定转导中的运动是由非常小的内部位移引起的S-1的全球自转(目前的“标准模型”)，还是内部运动包括S-1的大部分(与域间运动一样)。将作出努力-使用差示扫描量热法圆二色谱-以获得结构域结构的指示，并检查交联剂对这些结构域假定运动的影响。为了简化上述研究，还将尝试开发物理模型(S-1关于定向纯F-肌动蛋白)和分子图形模型。除了六名高级调查人员外，还有几名学生和年轻的助理将参与这项工作。这项建议的主要意义是基本的。由于生物能量换能器尚未被解释，因此发现设计特征的可能性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.