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An adaptor protein network that controls general and regulated proteolysis in Bacillus subtilis

控制枯草芽孢杆菌中一般和调节蛋白水解的接头蛋白网络

基本信息

批准号：
116735081
负责人：
Professor Dr. Kürsad Turgay
金额：
--
依托单位：
Max-Planck-Forschungsstelle für die Wissenschaft der Pathogene
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/116735081?language=en
关键词：
adaptor protein network controls general

项目摘要

Protein quality control systems are essential to ensure cellular protein homeostasis and monitor the folding and active state of proteins in all cells. These highly conserved systems include chaperone systems but also AAA+ protease complexes such as Hsp100/Clp proteins in bacteria. The ability to rescue and repair functional proteins by chaperones and/or to remove potentially toxic misfolded protein species by degradation could be considered as two branches of the same cellular protein quality control system. Interestingly, the same AAA+ protease systems are concurrently involved in the signal transduction and control of cellular and developmental processes by regulatory proteolysis of e.g. transcription factors. Proteolysis is mediated by dedicated molecular machines, which are formed by ringforming hexameric AAA+ motor proteins, associated with compartmentalized barrel-like peptidases. Examples for such proteolytic complexes are the proteasome in eukaryotic cells or the prokaryotic Hsp100/Clp proteins interacting with ClpP. Often the same proteolytic machines are used in addition for regulatory purposes, e.g. like regulated proteolysis of key transcription factors to control for example developmental processes. We are interested to understand how in prokaryotic cells the important and terminal cellular decision to degrade a protein for distinct and different regulatory or protein quality control reasons is taken. ClpCP of the soil bacterium Bacillus subtilis is involved in general protein quality control and regulatory processes. We could demonstrate for ClpCP that adaptor proteins like MecA, YpbH or McsB are necessary to activate the ClpCP protease and important for substrate recognition and selection. Based on our recent results we propose to address two interesting and new aspects of this system in more detail. (1) We want to investigate and possibly understand the interplay between the unfolding or remodeling and proteolytic mode of the Hsp100/Clp proteins both in vivo and in vitro. (2) We want to investigate the role and function of the adaptor protein mediated ClpC activation with a special emphasis on the protein arginine kinase McsB. We will test our hypothesis concerning the potential role of McsB in protein disaggregation using various in vivo and in vitro experiments.

蛋白质质量控制系统对于确保细胞蛋白质的动态平衡和监测所有细胞中蛋白质的折叠和活性状态是必不可少的。这些高度保守的系统包括伴侣系统，但也包括AAA+蛋白酶复合体，如细菌中的Hsp100/CLP蛋白。通过伴侣抢救和修复功能蛋白质和/或通过降解去除潜在的有毒错误折叠蛋白质物种的能力可以被认为是同一细胞蛋白质质量控制系统的两个分支。有趣的是，同样的AAA+蛋白水解酶系统通过调节转录因子的蛋白分解，同时参与细胞和发育过程的信号转导和控制。蛋白质分解是由专用的分子机器介导的，这些机器是由环状形成的六聚体AAA+马达蛋白与分隔的桶状多肽酶相关形成的。这种蛋白分解复合体的例子是真核细胞中的蛋白酶体或与ClpP相互作用的原核生物Hsp100/CLP蛋白。通常，相同的蛋白水解机还用于调节目的，例如，调节关键转录因子的蛋白分解，以控制例如发育过程。我们感兴趣的是，在原核细胞中，由于不同的调控或蛋白质质量控制的原因，细胞如何做出降解蛋白质的重要的和最终的决定。枯草芽孢杆菌的ClpCP参与蛋白质的一般质量控制和调控过程。我们可以证明对于ClpCP来说，MecA、YpbH或MCSB等适配蛋白是激活ClpCP蛋白酶所必需的，并且对于底物识别和选择是重要的。根据我们最近的结果，我们建议更详细地讨论这一系统的两个有趣和新的方面。(1)我们想要研究并可能了解Hsp100/CLP蛋白在体内和体外的去折叠或重塑与蛋白降解模式之间的相互作用。(2)我们想要研究接头蛋白介导的ClpC激活的作用和功能，特别是精氨酸激酶MCSB。我们将通过各种体内和体外实验来验证我们关于MCSB在蛋白质解聚中的潜在作用的假设。