New principle-based technologies for identifying transient protein interactions

描述(由申请人提供) 摘要：由于高通量DNA测序技术的进步，所有重要模式生物的基因组序列现在都是可用的。了解生物学和疾病的下一步是确定蛋白质相互作用组。然而，与基因组不同的是，蛋白质相互作用组是动态的，包含弱相关成分，这击中了当前技术的盲点。因此，为了构建一个完整的人类相互作用组，我建议开发一种新的基于原理的标记和识别强相互作用蛋白和弱相互作用蛋白的技术。这项新技术将在GPCRs的去孤构化、泛素E3连接酶底物的鉴定和伴侣网络的鉴定中得到展示。 与公共健康相关：蛋白质-蛋白质相互作用网络是大多数细胞过程的基础。为了了解生物学和疾病，并确定新的治疗靶点，拟议的新技术旨在搜索、分析和可视化蛋白质-蛋白质相互作用网络。

DESCRIPTION (Provided by the applicant) Abstract: Genome sequences of all important model organisms are now available, thanks to technological advances in high throughput DNA sequencing. The next step in understanding biology and disease is to identify protein interactome. However, unlike the genome, protein interactome is dynamic and contains weakly associated components, which hit the blind spots of current technologies. Hence, toward construction of a complete human interactome, I propose to develop a new principle-based technology for labeling and identifying both strongly and weakly interacting proteins. This new technology will be demonstrated in deorphanization of GPCRs, identification of substrates of ubiquitin E3 ligases, and identification of chaperon networks. Public Health Relevance: Protein-protein interaction networks underlie most cellular processes. To understand biology and disease and to identify new therapeutic targets, the proposed new technology aims to search, analyze and visualize protein-protein interaction networks.