STRUCTURAL BIOLOGY OF CYTOSKELETAL REGULATION

本项目侧重于若干结构性决定因素 负责调节肌动蛋白的组装特性 细胞骨架和这些活动的体内后果。 之一 肌动蛋白丝组装的主要特征， 目前了解的是ATP水解作用的机制， 肌动蛋白聚合 在X9 B，我们现在已经获得了高分辨率 数据的Mg-ATP酵母肌动蛋白和Mg-ATP和Mg-ADP形式的 网骨藻肌动蛋白。 在1.9E处，酵母结构清晰 显示了腺嘌呤核苷酸和八面体配位的 镁离子，以及水分子定位作为 攻击亲核体 此外，广泛的供水网络 在肌动蛋白单体的大裂缝中发现了分子， 可能在调节构象重排中起重要作用 这发生在长丝伸长时。 这些结构将为 第一次允许肌动蛋白催化的ATP水解被处理， 真正的酶反应。

This project focuses on a number of structural determinants responsible for regulating the assembly properties of the actin cytoskeleton and the in vivo consequences of these activities. One of the principle features of actin filament assembly that is not currently understood is the mechanism by which ATP hydrolysis effects actin polymerization. At X9B, we have now obtained high resolution data of Mg-ATP yeast actin and both the Mg-ATP and Mg-ADP forms of Dictyostelium actin. The yeast structure refined at 1.9E clearly shows the adenine nucleotide and the octahedral coordination of the magnesium ion, as well as a water molecule positioned to act as the attacking nucleophile. Furthermore, an extensive network of water molecules is revealed in the large cleft of the actin monomer that might be important in modulating the conformational rearrangements that occur upon filament elongation. These structures will for the first time allow for actin catalyzed ATP hydrolysis to be treated a true enzymatic reaction.