Jiang Jiansen, Zhang Xuefeng, Chen Yong, Wu Yi, Zhou Z Hong, Chang Zengyi, Sui Sen-Fang
Department of Biological Sciences and Biotechnology, State-Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China.
Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11939-44. doi: 10.1073/pnas.0805464105. Epub 2008 Aug 12.
Cells use molecular chaperones and proteases to implement the essential quality control mechanism of proteins. The DegP (HtrA) protein, essential for the survival of Escherichia coli cells at elevated temperatures with homologues found in almost all organisms uniquely has both functions. Here we report a mechanism for DegP to activate both functions via formation of large cage-like 12- and 24-mers after binding to substrate proteins. Cryo-electron microscopic and biochemical studies revealed that both oligomers are consistently assembled by blocks of DegP trimers, via pairwise PDZ1-PDZ2 interactions between neighboring trimers. Such interactions simultaneously eliminate the inhibitory effects of the PDZ2 domain. Additionally, both DegP oligomers were also observed in extracts of E. coli cells, strongly implicating their physiological importance.
细胞利用分子伴侣和蛋白酶来实现蛋白质至关重要的质量控制机制。DegP（HtrA）蛋白对大肠杆菌细胞在高温下的存活至关重要，几乎在所有生物中都发现了其同源物，它独特地兼具这两种功能。在此，我们报告了一种DegP通过与底物蛋白结合后形成大型笼状12聚体和24聚体来激活这两种功能的机制。冷冻电子显微镜和生化研究表明，这两种寡聚体均由DegP三聚体模块通过相邻三聚体之间的PDZ1-PDZ2成对相互作用持续组装而成。这种相互作用同时消除了PDZ2结构域的抑制作用。此外，在大肠杆菌细胞提取物中也观察到了这两种DegP寡聚体，这有力地表明了它们的生理重要性。
