Crystal structure of Arabidopsis Deg2 protein reveals an internal PDZ ligand locking the hexameric resting state.
Crystal structure of Arabidopsis Deg2 protein reveals an internal PDZ ligand locking the hexameric resting state.
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DOI：
10.1074/jbc.m112.394585
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发表时间：
2012-10-26
期刊：
影响因子：
--
通讯作者：
Liu L
中科院分区：
文献类型：
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作者：
Sun R;Fan H;Gao F;Lin Y;Zhang L;Gong W;Liu L
背景：PDZ蛋白酶Deg2通过一种未知的分子机制参与叶绿体蛋白质量控制。结果：一个具有内部配体的新型PDZ结构域介导六聚体的形成，并将Deg2锁定在静息状态。结论：静息六聚体的形成可能是Deg蛋白酶亚家族的共同策略。意义：我们提供了PDZ结构域介导的Deg蛋白酶调控的结构见解。真核细胞器已经发展出复杂的蛋白质质量控制系统以确保其正常活动，其中Deg/HtrA蛋白酶起着至关重要的作用。植物Deg2蛋白酶是原核生物DegQ/DegP蛋白酶的同源物，位于叶绿体基质中，其蛋白水解活性是在逆境中维持光合机制效率所必需的。在这里，我们证明了Deg2具有双蛋白酶伴侣活性，并且我们提出了Deg2与共纯化肽络合的六聚体结构。结构表明，Deg2在常规PDZ结构域（PDZ1）之后包含一个独特的第二PDZ结构域（PDZ2），其中PDZ2编排了Deg2的笼形组装。我们发现了PDZ2的一个保守的内部配体，它介导六聚体的形成，从而将蛋白酶锁定在静息状态。这些发现提供了对PDZ结构域介导的Deg蛋白酶调节的不同模式的见解。
Background: The PDZ protease Deg2 is involved in chloroplast protein quality control through a yet unknown molecular mechanism. Results: A novel PDZ domain with an internal ligand mediates hexamer formation and locks Deg2 into the resting state. Conclusion: Formation of the resting hexamer may be a common strategy in a Deg protease subfamily. Significance: We provide structural insights into the PDZ domain-mediated regulation of Deg proteases. Eukaryotic organelles have developed elaborate protein quality control systems to ensure their normal activity, among which Deg/HtrA proteases play an essential role. Plant Deg2 protease is a homologue of prokaryotic DegQ/DegP proteases and is located in the chloroplast stroma, where its proteolytic activity is required to maintain the efficiency of photosynthetic machinery during stress. Here, we demonstrate that Deg2 exhibits dual protease-chaperone activities, and we present the hexameric structure of Deg2 complexed with co-purified peptides. The structure shows that Deg2 contains a unique second PDZ domain (PDZ2) following a conventional PDZ domain (PDZ1), with PDZ2 orchestrating the cage assembly of Deg2. We discovered a conserved internal ligand for PDZ2 that mediates hexamer formation and thus locks the protease in the resting state. These findings provide insight into the diverse modes of PDZ domain-mediated regulation of Deg proteases.