Investigating the Structural Mechanisms and Features of KCTD9

KCTD9的结构机制和特征研究

• 批准号: 2446332
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2446332
• 关键词: Investigating; Structural; Mechanisms; Features; KCTD9

Eukaryotic cells use the ubiquitin proteosome system to degrade proteins and regulate their activity. E3 ligases are a class of proteins which act as a key component for this process. Recently, these proteins have received interest in several medicinal and biological research fields. The primary project will seek to determine the structure of KCTD9 by x-ray crystallography and identify substrate proteins with affinity proteomics. The structural features which govern the interactions between the E3 ligase and these substrates will then be characterized. The ubiquitination activity, the cellular role, and the implication KCTD9 has on natural killer cell development will also be explored. A secondary project will aim to develop a novel chemical probe for a different cullin RING ligase, FBXO31. The structural data of FBXO31 will aid the development and optimization of this probe. The probe will then be validated for in vitro study of FBXO31 and additional functions can be examined.BBSRC will give priority to fundamental science which addresses important underpinning questions in biology or normal human physiology, which can advance knowledge and innovation across many sectors.

真核细胞利用泛素蛋白体系统降解蛋白质并调节其活性。E3连接酶是这一过程中起关键作用的一类蛋白质。近年来，这些蛋白在一些医学和生物学研究领域引起了人们的兴趣。主要项目将寻求通过x射线晶体学确定KCTD9的结构，并通过亲和蛋白质组学鉴定底物蛋白。控制E3连接酶与这些底物之间相互作用的结构特征将被表征。KCTD9的泛素化活性、细胞作用以及对自然杀伤细胞发育的影响也将被探讨。第二个项目将致力于开发一种新的化学探针，用于检测不同的cullin RING连接酶FBXO31。FBXO31的结构数据将有助于该探针的开发和优化。然后，该探针将用于FBXO31的体外研究，并可以检查其他功能。BBSRC将优先考虑解决生物学或正常人体生理学中重要基础问题的基础科学，这可以推动许多领域的知识和创新。