Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins
Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins
复制标题
通过与底物蛋白结合后形成大的笼状寡聚物来激活 DegP 分子伴侣蛋白酶
DOI：
10.1073/pnas.0805464105
复制
发表时间：
2008-08-19
影响因子：
11.1
通讯作者：
Sui, Sen-Fang
中科院分区：
文献类型：
--
作者：
Jiang, Jiansen;Zhang, Xuefeng;Sui, Sen-Fang
细胞利用分子伴侣和蛋白酶来实现蛋白质的基本质量控制机制。DegP （HtrA）蛋白是大肠杆菌细胞在高温下存活所必需的，几乎在所有生物体中都发现了它的同源物，它独特地具有这两种功能。在这里，我们报告了DegP在与底物蛋白结合后通过形成大的笼状12-和24-mers来激活这两种功能的机制。低温电镜和生化研究表明，这两种低聚物都是通过相邻三聚体之间的PDZ1-PDZ2相互作用，由DegP三聚体块一致地组装而成的。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这两种DegP低聚物，这强烈暗示了它们的生理重要性。
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.