Chemical staples and chemical probes to dissect dynamins cellular roles.

蛋白质结构的调节驱动细胞功能。动力蛋白GTPase形成至少两种具有不同细胞功能的大分子结构。这些不同结构背后的驱动因素尚不清楚。在这个项目中，我们将利用我们的发现和计划的改进，化学生物学探针将通过抑制三个不同的位点来调节动力蛋白活性，一个位点刺激动力蛋白活性。众所周知，动力蛋白螺旋和环被认为至少负责三种细胞生物学功能：激素、中性和受体内化；细胞有丝分裂和肌动蛋白动力学。在这项工作之前，我们缺乏工具来理解形状调节蛋白质功能的作用。

Modulation of protein structure drives cellular function. Dynamin GTPase forms at least two macromolecular structures with different cellular functions. The drivers behind these different structures is unknown. In this project we will leverage our discoveries, and planned enhancements, of chemical biology probes that will modulate dynamin activity by inhibiting at three distinct sites, and one site that stimulates dynamin activity. It is known that Dynamin helices and rings are believed responsible for at least three in cell biological functions: in hormone, neutral and receptor internalisation; cellular mitosis and in actin dynamics. Prior to this work we have lacked the tools to understand the role of shape modulation of protein function.