Understanding endogenous allosteric modulators of G protein-coupled receptors

了解 G 蛋白偶联受体的内源性变构调节剂

• 批准号: FT140100114
• 负责人: Dr Celine Valant
• 金额: $ 53.11万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: ARC Future Fellowships
• 财政年份: 2014
• 资助国家: 澳大利亚
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/FT140100114
• 关键词: Understanding; endogenous; allosteric; modulators; protein

Major life science challenges include how chemicals outside cells signal to proteins inside, how this results in physiological responses, and how dysfunction of these processes leads to pathophysiology. Despite the critical importance of G protein-coupled receptors (GPCRs), much remains to be learned about their regulation by endogenous and synthetic molecules. This project aims to address this gap, by building on recent ground-breaking studies that have been performed, by focusing on alternative binding sites of GPCRs called allosteric sites. The major hypothesis is that these allosteric sites are widespread across GPCRs because the body produces endogenous allosteric ligands that remain largely unidentified, but which can play vital roles in biology.

主要的生命科学挑战包括细胞外的化学物质如何向细胞内的蛋白质发出信号，这如何导致生理反应，以及这些过程的功能障碍如何导致病理生理学。尽管G蛋白偶联受体（gpcr）至关重要，但内源性和合成分子对其调控的研究仍有待深入。该项目旨在解决这一差距，通过建立最近已经进行的突破性研究，通过关注gpcr的替代结合位点，即变构位点。主要的假设是，这些变构位点在gpcr中广泛存在，因为人体产生内源性变构配体，这些配体在很大程度上仍未被识别，但在生物学中起着至关重要的作用。