权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

A systematic structural-based approach to studying protein interactions in the centriole/centrosome

一种基于结构的系统方法来研究中心粒/中心体中的蛋白质相互作用

基本信息

批准号：
2734924
负责人：
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：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2734924
关键词：
systematic structural based approach studying

项目摘要

Centrosomes are required for cell division, cilia formation, cytoskeletal organisation and cell signalling, and their dysfunction leads to a range of human diseases, including cancer. Centrosomes are complicated structures comprising >400 proteins, but only a small, well-conserved, group of proteins are required for centrosome assembly. The protein interactions mediating assembly are mostly unknown. While previous work studying protein interactions has often relied on relatively slow and laborious techniques such as X-ray crystallography, recent advances allow for the much faster computational prediction of 3D interaction structures. Experimental work testing these predictions can then be targeted to specific interfaces.This project aims to identify and characterise interactions between the small set of core centrosome proteins required for centrosome assembly. Interactions will first be predicted computationally, and predictions scoring above a specified confidence threshold will be assessed experimentally. In parallel with this, various methods will be tested to develop a pipeline optimisedfor speed and accuracy of protein interaction prediction and validation.Overall, this work will increase our knowledge of the structural basis of interactions involved in centrosome assembly, as well as developing new methodology to enable this approach to be expanded to other candidate proteins involved in other biological processes.BBSRC priority areas: - Understanding the rules of life- Transformative technologies

中心体是细胞分裂、纤毛形成、细胞骨架组织和细胞信号传递所必需的，它们的功能障碍导致包括癌症在内的一系列人类疾病。中心体是一种复杂的结构，由大约400种蛋白质组成，但中心体的组装只需要一小部分保守的蛋白质。介导组装的蛋白质相互作用大多是未知的。虽然以前研究蛋白质相互作用的工作通常依赖于相对缓慢和费力的技术，如x射线晶体学，但最近的进展允许对3D相互作用结构进行更快的计算预测。测试这些预测的实验工作可以针对特定的界面。该项目旨在确定和表征中心体组装所需的一小组核心中心体蛋白之间的相互作用。相互作用将首先进行计算预测，并且预测得分高于指定的置信度阈值将进行实验评估。与此同时，将测试各种方法，以开发优化蛋白质相互作用预测和验证的速度和准确性的管道。总的来说，这项工作将增加我们对中心体组装中相互作用的结构基础的了解，并开发新的方法，使这种方法扩展到参与其他生物过程的其他候选蛋白质。BBSRC的优先领域：-理解生活规则-变革性技术