Proc Natl Acad Sci U S A，2008, 105(33):11939-11944.
Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins
Jiansen Jiang*,†, Xuefeng Zhang*,†,‡, Yong Chen*, Yi Wu§, Z. Hong Zhou¶,‖, Zengyi Chang‡,**, and Sen-Fang Sui*,**
*Department of Biological Sciences and Biotechnology, State-Key Laboratory of Biomembrane and Membrane Biotechnology, Tsinghua University, Beijing 100084, China; ‡School of Life Sciences, National Laboratory of Protein Engineering and Plant Genetic Engineering, Center for Protein Science, Peking University, Beijing 100871, China; §Institute of Biophysics, Lanzhou University, Lanzhou 730000, China; and ¶Department of Pathology and Laboratory Medicine, University of Texas Medical School, Houston, TX 77030; and ‖Department of Microbiology, Immunology, and Molecular Genetics and California NanoSystems Institute, University of California, Los Angeles, CA 90095-1594
Edited by Robert T. Sauer, Massachusetts Institute of Technology, Cambridge, MA, and approved June 19, 2008
†J.J. and X.Z. contributed equally to this work. (received for review June 6, 2008)
Abstract
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.
Author contributions: J.J., X.Z., Z.C., and S.-F.S. designed research; J.J., X.Z., and Y.C. performed research; J.J., X.C., Y.W., and Z.H.Z. analyzed data; and J.J., Z.C., and S.-F.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
© 2008 by The NationalAcademy of Sciences of the USA
论文题目和摘要的中文翻译：
题目：DegP分子伴侣-蛋白质水解酶通过结合底物蛋白并形成笼状寡聚体而被激活
摘要：细胞对蛋白质的质量控制是生命过程的关键机制之一，这是通过分子伴侣和蛋白质水解酶这两类蛋白质的功能而具体实现的。而DegP（又称HtrA）这种其同源体几乎存在于所有的生物中、对于大肠杆菌在高温下的生存不可或缺的蛋白质非常独特地将两种功能合二为一。在此文中，我们报道了DegP在结合底物蛋白质后通过形成大的笼状12聚体或24聚体而激活其两种生物学功能的机制。冰冻电子显微镜和生物化学研究结果揭示，两种同源寡聚体皆利用三聚体板块单位组装而成，且都是通过位于一个三聚体上的亚基的PDZ1结构域与其相邻的三聚体上的另一个亚基的PDZ2结构域之间的成对相互作用而介导。这样的相互作用模式同时将PDZ2结构域先前对蛋白质活性的抑制效应消除了。我们在大肠杆菌细胞的抽提物中也观察到了DegP 这两种寡聚体形式的存在，强烈暗示它们是具有生理学意义的。
简单评语：该工作是由江健森（隋森芳指导的博士生）和张雪峰（昌增益指导的博士生）联合完成的。它不仅揭示了蛋白质水解酶激活的一种全新机制（不是通过传统所认识的酶切激活，而是通过一种底物诱导的、可逆的同源寡化过程），同时也为“蛋白质的生物学活性可以通过同源寡聚化而有效调节”这一结论提供了新的证据。
