Functional Characterization of Unconventional Myosin Motors

以前的工作使我们能够将特定突变引入肌球蛋白运动域的结构变化与化学机械能量转导的机制以及1类和2类肌球蛋白的体内和体外功能联系起来。在拟议工作的背景下，我们的目标是将我们工作的主要重点从先前工作中专门使用的Dictyostelials模型系统转移到哺乳动物肌球蛋白的研究上。具体地说，我们将描述MyoG和哺乳动物肌球蛋白的结构和功能特性，MyoG在Dictyostelials发育的所有阶段都会产生，而哺乳动物的肌球蛋白属于16和18类。16类肌球蛋白在神经组织发育中最突出，可能与1类肌球蛋白具有一些相同的功能特性。第18类肌球蛋白的产生相当普遍。它们形成重链二聚体，它们是否可以充当分子马达是值得怀疑的。所有三种类型的肌球蛋白都含有运动域以外的蛋白质相互作用域。我们进入这些研究的长期目标是阐明运动介导的运输过程和化学信号事件之间的联系。

Previous work allowed us to link structural alterations introduced by specific mutations into the myosin motor domain to the mechanism of chemomechamcal energy transduction and the in vivo and in vitro functions of class-1 and class-2 myosins. Within the context of the proposed work we aim to shift the main focus of our work from the Dictyostelium model system, which was used exclusively in previous work, to the study of mammalian myosins. Specifically, we will characterise the structural and functional properties of MyoG, which is produced during all stages of Dictyostelium development, and mammalian myosins belonging to classes 16 and 18. Class 16 myosins are most prominent in developing neural tissue and are likely to share some of their functional properties with class-1 myosins. Class 18 myosins are produced rather ubiquitously. They form heavy chain dimers and it is questionable whether they can act as molecular motors. All three types of myosins contain protein interaction domains outside the motor domain. Our long term goal in entering these studies is the elucidation of connections between motor mediated transport processes and chemical signalling events.