Chemical staples and chemical probes to dissect dynamins cellular roles.

用于剖析动力细胞作用的化学钉书和化学探针。

• 批准号: DP240100514
• 负责人: Prof Adam McCluskey
• 金额: $ 70.28万
• 依托单位: The University of Newcastle
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2024
• 资助国家: 澳大利亚
• 起止时间: 2024-01-01 至 2028-12-31
• 项目状态: 未结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP240100514
• 关键词: Chemical; staples; chemical; probes; dissect

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.

蛋白质结构的调节驱动细胞功能。 Dynamin GTPase至少形成两个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，我们将利用化学生物学探针的发现和计划的增强，这些探针将通过抑制三个不同的位点来调节动力蛋白活性，而一个刺激动力蛋白活性的位点。众所周知，据信动力蛋白螺旋和环在细胞生物学功能上至少造成三个：激素，中性和受体内在化；细胞有丝分裂和肌动蛋白动力学。在这项工作之前，我们缺乏了解蛋白质功能的形状调节作用的工具。