Structural and Functional Analysis of Bacterial and Viral Deubiquitinases

细菌和病毒去泛素酶的结构和功能分析

• 批准号: RGPIN-2017-05985
• 负责人: Saridakis, Vivian
• 金额: $ 1.89万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=629197
• 关键词: Structural; Functional; Analysis; Bacterial; Viral

Ubiquitin signalling is critical in many cellular processes. The covalent attachment of ubiquitin to substrate proteins affects their biological functions. The best characterized function is 26S mediated proteasomal degradation of the substrate protein. Ubiquitin is attached to substrate proteins through an enzymatic cascade consisting of E1, E2 and E3 enzymes. Ubiquitin can also be cleaved from substrate proteins by deubiquitinases (DUBs). Deubiquitination activity must be highly regulated otherwise proteins would be targeted by these enzymes non-specifically resulting in deregulated cellular processes. Pathogenic organisms have the ability to manipulate ubiquitin signalling in host organisms to their advantage. This is a critical step in invasion by the pathogen. A variety of pathogenic organisms including bacteria and viruses possess proteins involved in ubiquitin signalling including bacterial/viral E3 ligases and DUBs that are used to dampen the immune response to enable infection.

泛素信号传导在许多细胞过程中至关重要。泛素与底物蛋白的共价连接影响其生物学功能。最好的功能是26 S介导的底物蛋白的蛋白酶体降解。泛素通过由E1、E2和E3酶组成的酶级联反应与底物蛋白质连接。泛素还可以通过去泛素化酶（DUB）从底物蛋白质切割。去泛素化活性必须受到高度调节，否则蛋白质将被这些酶非特异性地靶向，导致细胞过程失调。病原生物体有能力操纵宿主生物体中的泛素信号传导，使其对自己有利。这是病原体入侵的关键步骤。包括细菌和病毒在内的多种病原体具有参与泛素信号传导的蛋白质，包括细菌/病毒E3连接酶和DUB，其用于抑制免疫应答以使感染成为可能。