Mdm38 is a 14-3-3-Like Receptor and Associates with the Protein Synthesis Machinery at the Inner Mitochondrial Membrane
Mdm38 is a 14-3-3-Like Receptor and Associates with the Protein Synthesis Machinery at the Inner Mitochondrial Membrane
复制标题
DOI：
10.1111/j.1600-0854.2011.01239.x
复制
发表时间：
2011-10-01
期刊：
影响因子：
4.5
通讯作者：
Rehling, Peter
中科院分区：
文献类型：
--
作者：
Lupo, Domenico;Vollmer, Christine;Rehling, Peter
线粒体核糖体合成内膜呼吸链复合物的核心亚基。在线粒体中，翻译受到 mRNA 特异性激活蛋白的调节，并发生在膜相关核糖体上。 Mdm38/Letm1 是线粒体核糖体的保守膜受体，特别参与呼吸链生物发生。此外，Mdm38 及其高等真核同源物 Letm1 在内膜中充当 K+/H+ 或 Ca2+/H+ 逆向转运蛋白。在这里，我们鉴定了 Mdm38 的保守核糖体结合域 (RBD)，并以 2.1 埃分辨率确定了晶体结构。令人惊讶的是，Mdm38(RBD) 显示出 14-3-3 样折叠，尽管在一级序列水平上与 14-3-3 蛋白有任何相似性，因此代表了线粒体中第一个 14-3-3 样蛋白。 14-3-3 样结构域通过调节 Cox1 和 Cytb 翻译对于呼吸链组装至关重要。我们证明该功能可以在空间上与 Mdm38 膜集成部分的离子传输活性分离。根据观察到的 mdm38 Delta 与缺乏 RBD 的 Mdm38 的表型，我们提出了一种模型，将离子转运和翻译调节结合到一个分子中，允许跨内膜的离子流直接耦合，并通过其与蛋白质合成机制的直接关联作为线粒体膜蛋白翻译的信号。
Mitochondrial ribosomes synthesize core subunits of the inner membrane respiratory chain complexes. In mitochondria, translation is regulated by mRNA-specific activator proteins and occurs on membrane-associated ribosomes. Mdm38/Letm1 is a conserved membrane receptor for mitochondrial ribosomes and specifically involved in respiratory chain biogenesis. In addition, Mdm38 and its higher eukaryotic homolog Letm1, function as K+/H+ or Ca2+/H+ antiporters in the inner membrane. Here, we identify the conserved ribosome-binding domain (RBD) of Mdm38 and determine the crystal structure at 2.1 angstrom resolution. Surprisingly, Mdm38(RBD) displays a 14-3-3-like fold despite any similarity to 14-3-3-proteins at the primary sequence level and thus represents the first 14-3-3-like protein in mitochondria. The 14-3-3-like domain is critical for respiratory chain assembly through regulation of Cox1 and Cytb translation. We show that this function can be spatially separated from the ion transport activity of the membrane integrated portion of Mdm38. On the basis of the phenotypes observed for mdm38 Delta as compared to Mdm38 lacking the RBD, we suggest a model that combining ion transport and translational regulation into one molecule allows for direct coupling of ion flux across the inner membrane, and serves as a signal for the translation of mitochondrial membrane proteins via its direct association with the protein synthesis machinery.