Structure-function analysis of DegP

DegP的结构功能分析

• 批准号: 73451336
• 负责人: Professor Dr. Michael Ehrmann
• 金额: --
• 依托单位: Zentrum für Medizinische Biotechnologie (ZMB)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/73451336?language=en
• 关键词: Structure; function; analysis; DegP

The widely conserved HtrA family of serine proteases is involved in extracytoplasmic protein quality control. Two well studied family members, E. coli DegP and DegS are key players of the unfolded protein response performing protective and regulatory roles. DegS senses protein folding defects and initiates a signaling cascade that controls the activity of dozens of stress promoters including degP. DegP switches between molecular chaperone and protease functions channelling damaged proteins into either repair or degradation pathways. Recent work revealed that DegP switches also between three oligomeric states (hexamer, 12 and 24mer) and that different functional and architectural features might be interconnected. This research proposal aims at characterising in detail the underlying molecular mechanisms determining the switch of oligomeric state and their physiological consequences using genetic, biochemical and structural approaches. These studies will contribute to our understanding of the general principles of stress sensing, protein repair and degradation in the bacterial cell envelope.

广泛保守的丝氨酸蛋白酶HtrA家族参与胞质外蛋白质的质量控制。两个很好的研究家庭成员，E。大肠杆菌DegP和DegS是未折叠蛋白反应的关键参与者，执行保护和调节作用。DegS检测蛋白质折叠缺陷并启动信号级联反应，控制包括degP在内的数十种应激启动子的活性。DegP在分子伴侣和蛋白酶功能之间切换，将受损蛋白引导到修复或降解途径中。最近的工作表明，DegP开关之间的三个寡聚状态（六聚体，12和24聚体），不同的功能和建筑特征可能是相互关联的。这项研究计划旨在利用遗传、生物化学和结构方法，详细描述决定寡聚状态转换及其生理后果的潜在分子机制。这些研究将有助于我们理解细菌细胞膜中的压力传感、蛋白质修复和降解的一般原理。

项目成果

Chemical Biology Approaches Reveal Conserved Features of a C‐Terminal Processing PDZ Protease

• DOI: 10.1002/cbic.201100643
• 发表时间: 2012-02
• 期刊: ChemBioChem
• 影响因子: 3.2
• 作者: Juliane Weski;M. Meltzer;Lina Spaan;T. Mönig;Julian Oeljeklaus;P. Hauske;Lars Vouillème;R. Volkmer;P. Boisguérin;D. Boyd;R. Huber;M. Kaiser;M. Ehrmann

Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis

• DOI: 10.1111/mmi.12306
• 发表时间: 2013-08-01
• 期刊: MOLECULAR MICROBIOLOGY
• 影响因子: 3.6
• 作者: Gloeckl, Sarina;Ong, Vanissa A.;Huston, Wilhelmina M.
• 通讯作者: Huston, Wilhelmina M.