The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel localized to the inner mitochondrial membrane. Here, we describe the structure of an MCU orthologue from the fungus Neosartorya fischeri (NfMCU) determined to 3.8 Å resolution by phase-plate cryo-electron microscopy. The channel is a homotetramer with two-fold symmetry in its amino-terminal domain (NTD) that adopts a similar structure to that of human MCU. The NTD assembles as a dimer of dimers to form a tetrameric ring that connects to the transmembrane domain through an elongated coiled-coil domain. The ion-conducting pore domain maintains four-fold symmetry, with the selectivity filter positioned at the start of the pore-forming TM2 helix. The aspartate and glutamate sidechains of the conserved DIME motif are oriented towards the central axis and separated by one helical turn. The structure of NfMCU offers insights into channel assembly, selective calcium permeation, and inhibitor binding.A cryo-electron microscopy structure of fungal mitochondrial calcium uniporter shows that the channel is tetrameric and sheds light on channel assembly and function.

中文翻译：

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真菌线粒体钙单向转运体的冷冻电镜结构

线粒体钙单向转运蛋白 (MCU) 是一种高度选择性的钙通道，位于线粒体内膜。在这里，我们描述了来自真菌 Neosartorya fischeri (NfMCU) 的 MCU 直向同源物的结构，该同源物通过相位板冷冻电子显微镜确定为 3.8 Å 分辨率。该通道是一个同源四聚体，其氨基末端结构域 (NTD) 具有双重对称性，采用与人类 MCU 相似的结构。NTD 组装成一个二聚体的二聚体，形成一个四聚体环，通过一个细长的卷曲螺旋结构域连接到跨膜结构域。离子传导孔域保持四重对称，选择性过滤器位于成孔 TM2 螺旋的起点。保守的 DIME 基序的天冬氨酸和谷氨酸侧链朝向中心轴并由一个螺旋圈分开。NfMCU 的结构提供了对通道组装、选择性钙渗透和抑制剂结合的见解。真菌线粒体钙单向转运蛋白的冷冻电子显微镜结构显示该通道是四聚体，并揭示了通道组装和功能。