Metabolite Sensing and Regulation of Protein Function

蛋白质功能的代谢传感和调节

• 批准号: 9912164
• 负责人: Hening Lin
• 金额: $ 39.23万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9912164
• 关键词: Address; Area; Biological Process; Biology; Biomedical Research; Cells; Chemicals; Enzymes; Gene Expression; Glutathione; Human Genome; Investigation; Laboratories; Life; Mammalian Cell; Metabolic Pathway; Nicotinamide adenine dinucleotide; Organism; Play; Post-Translational Protein Processing; Process; Proteins; Regulation; Research; Research Support; Role; Science; Signal Transduction; Stress; Techniques; Therapeutic; inhibitor/antagonist; novel; protein function; response; small molecule; therapeutic development

Metabolite Sensing and Regulation of Protein Function After the human genome is sequenced, one of the most important challenges in biomedical research is to understand how gene expression changes in response to various signals and stresses. In other words, understanding cell signaling mechanisms is of critical importance to understand life processes. This proposal focuses on how mammalian cells sense certain metabolites and use that information to regulate protein function. Common cellular metabolites, such as co-enzyme A, glutathione, and nicotinamide adenine dinucleotides, play important roles in various metabolic pathways. Many protein post-translational modifications also use these metabolites. Maintaining the concentrations of these metabolites is thus critically important. Cells and organisms must be able to sense these metabolites and use the information to regulate biological processes. However, very little is known about the sensing mechanisms for these metabolites. In this MIRA application, I will focus on using chemical biology techniques to identify how mammalian cells sense common metabolites to regulate protein function. Preliminary results indicate that this is a highly interesting and exciting area that warrant much more investigation. This a completely new research direction for my laboratory and is distinct from my previous and HHMI-supported research. The proposed research will identify many novel regulatory mechanisms of protein function by small molecule metabolites. This will in turn provide a better understanding of cell signaling and address one of the most important challenges in biomedical sciences in the postgenomic era. These regulatory mechanisms can also directly impact the development of therapeutics as they will help to develop allosteric inhibitors or activators of proteins.

蛋白质功能的代谢传感和调节 人类基因组测序完成后，生物医学研究中最重要的挑战之一是 了解基因表达如何响应各种信号和压力而变化。换句话说， 了解细胞信号传导机制对于了解生命过程至关重要。这个提议 重点研究哺乳动物细胞如何感知某些代谢物并利用该信息来调节蛋白质功能。 常见的细胞代谢物，如辅酶 A、谷胱甘肽和烟酰胺腺嘌呤二核苷酸，发挥着 在多种代谢途径中发挥重要作用。许多蛋白质翻译后修饰也使用这些 代谢物。因此，维持这些代谢物的浓度至关重要。细胞和生物体 必须能够感知这些代谢物并利用这些信息来调节生物过程。然而， 人们对这些代谢物的传感机制知之甚少。在这个 MIRA 应用程序中，我将重点关注 使用化学生物学技术来确定哺乳动物细胞如何感知常见代谢物以进行调节 蛋白质功能。初步结果表明，这是一个非常有趣和令人兴奋的领域，值得大量研究 更多调查。这对我的实验室来说是一个全新的研究方向，与我之前的研究方向不同 和 HHMI 支持的研究。拟议的研究将确定蛋白质的许多新的调控机制 通过小分子代谢物发挥作用。这反过来将有助于更好地理解细胞信号传导和 解决后基因组时代生物医学最重要的挑战之一。这些监管 机制也可以直接影响治疗方法的发展，因为它们将有助于开发变构 蛋白质的抑制剂或激活剂。