Howard Hughes Medical Institute and Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature. 2018 Jul;559(7715):570-574. doi: 10.1038/s41586-018-0333-6. Epub 2018 Jul 11.
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.
线粒体钙单向转运体（MCU）是一种高度选择性的钙通道，位于线粒体内膜上。在这里，我们通过相衬 cryo-EM 描述了真菌 Neosartorya fischeri（NfMCU）的 MCU 同源物的结构，分辨率为 3.8Å。该通道是一个四聚体，在其氨基末端结构域（NTD）中具有二倍对称性，其结构类似于人类 MCU。NTD 组装成二聚体的二聚体，形成一个四聚体环，通过一个拉长的卷曲螺旋域与跨膜结构域连接。离子传导孔结构域保持四重对称性，选择性过滤器位于形成孔的 TM2 螺旋的起始处。保守的 DIME 基序的天冬氨酸和谷氨酸侧链朝向中心轴，彼此分隔一个螺旋圈。NfMCU 的结构为通道组装、选择性钙渗透和抑制剂结合提供了深入的了解。
