Structural studies of kinesin motor proteins (Strukturuntersuchung von Kinesin-Motorproteinen)

细胞运动的许多方面是由微管依赖的运动控制的，包括囊泡和细胞器的运输、内吞作用、鞭毛跳动和有丝分裂。有大量且数量不断增加的马达蛋白，专门用于不同的任务。在大多数情况下，他们的作用和运作模式是未知的。到目前为止，已经报道了五种运动蛋白样微管马达的晶体结构，其中包括我们实验室的两种(来自大鼠大脑的传统运动蛋白运动域的单体和二聚体)。这些结构揭示了动蛋白的一些性质，但仍未确定重要的问题，如步进机制、控制速度的元素、正向或反向的起源。这个项目的目的是通过解决不同类型的运动蛋白马达、在重要功能残基上突变的运动蛋白变体或不同功能状态的运动蛋白的晶体结构来解决这些问题。

Many aspects of cellular movement are governed by microtubuledependent motors, including vesicle and organelle transport, endocytosis, flagellar beating, mitosis. There is a large and growing number of motor proteins, specialized for different tasks. In most cases their roles and modes of operation are not known. Thus far, five crystal structures of kinesin-like microtubule motors have been reported, including two from our lab (conventional kinesin motor domain from rat brain in monomeric and dimeric form). The structures have revealed some properties of kinesins but left important questions undecided, such as the stepping mechanism, the elements controlling velocity, or the origin of forward or reverse directionality. The aim of this project is to approach these issues by solving crystal structures of different types of kinesin motors, of kinesin variants mutated at functionally important residues, or of kinesins in different functional states.