Motor mechanism of native ATPase complexes

AAA+超家族的ATP酶（与各种细胞活性相关的ATP酶）通常处于多蛋白质复合物的核心，负责以能量依赖性方式及时破坏或重塑大分子。它们形成最大的蛋白质超家族之一，是细胞内蛋白质、膜或DNA的大多数重组和再循环过程的关键组成部分。其独特的功能特异性来源于将高度保守的AAA+结构域与辅助结构域和促进AAA+活性微调的蛋白质相结合。本项目的目标是确定不同功能AAA+组装体的三维结构，以了解AAA+蛋白的共同潜在作用机制及其受辅助因子的调节。使用单粒子冷冻电子显微镜的功能状态（i）热休克蛋白（HSP）100的变体与不同大小的域插入，（ii）蛋白酶体亚复合物和（iii）异源寡聚过氧化物酶体ATP酶组件将进行探讨。

ATPases of the AAA+ superfamily (ATPases associated with various cellular activities) are often at the core of multi-protein complexes responsible for timely destruction or remodeling of macromolecules in an energy dependent manner. They form one of the largest protein superfamilies and are crucial components in most re-organization and recycling processes of protein, membrane or DNA within the cell. Their unique functional specificity derives from combining the highly conserved AAA+ domain with accessory domains and proteins which facilitate fine tuning of the AAA+ activity. The goal of this project is to determine the three dimensional structure of different functional AAA+ assemblies in order to understand the common underlying mechanism of action of AAA+ proteins and its regulation by accessory factors. Using single particle cryo electron microscopy the functional states of (i) heat shock protein (Hsp) 100 variants with varying sized domain insertions, (ii) proteasomal subcomplexes and (iii) hetero oligomeric peroxisomal ATPase assemblies will be explored.