The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Å and 3.2 Å resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers. The atomic model of C. europaea MCU shows that a conserved WDXXEP signature sequence forms the selectivity filter, in which calcium ions are arranged in single file. Coiled-coil legs connect the pore to N-terminal domains in the mitochondrial matrix. In C. europaea MCU, the N-terminal domains assemble as a dimer of dimers; in zebrafish MCU, they form an asymmetric crescent. The structures define principles that underlie ion permeation and calcium selectivity in this unusual channel.Structures of the mitochondrial calcium uniporter from fungal and metazoan organisms reveal a tetrameric architecture and shed light on the function of the channel.

中文翻译：

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真菌和后生动物线粒体钙单向转运体的冷冻电镜结构

线粒体钙单向转运体 (MCU) 是一种高度选择性的钙通道，是钙进入线粒体的主要途径。通道如何催化离子渗透并实现离子选择性尚不清楚，部分原因是 MCU 被认为与其他细胞通道相比具有独特的架构。在这里，我们报告了分别以 8.5 Å 和 3.2 Å 分辨率对斑马鱼和 Cyphellophora europaea 的 MCU 通道进行低温电子显微镜重建。与先前关于 MCU 的五聚体化学计量的报告相比，两个通道都是四聚体。C. europaea MCU 的原子模型表明，保守的 WDXXEP 签名序列形成选择性过滤器，其中钙离子排列成单行。盘绕的线圈腿将孔连接到线粒体基质中的 N 端结构域。在 C. europaea MCU，N 端域组装成二聚体的二聚体；在斑马鱼 MCU 中，它们形成一个不对称的新月形。这些结构定义了这个不寻常通道中离子渗透和钙选择性的基础原理。来自真菌和后生动物的线粒体钙单向转运体的结构揭示了四聚体结构，并阐明了通道的功能。