Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Science. 2018 Aug 3;361(6401):506-511. doi: 10.1126/science.aar4056. Epub 2018 Jun 28.
Calcium transport plays an important role in regulating mitochondrial physiology and pathophysiology. The mitochondrial calcium uniporter (MCU) is a calcium-selective ion channel that is the primary mediator for calcium uptake into the mitochondrial matrix. Here, we present the cryo-electron microscopy structure of the full-length MCU from to an overall resolution of ~3.7 angstroms. Our structure reveals a tetrameric architecture, with the soluble and transmembrane domains adopting different symmetric arrangements within the channel. The conserved W-D-Φ-Φ-E-P-V-T-Y sequence motif of MCU pore forms a selectivity filter comprising two acidic rings separated by one helical turn along the central axis of the channel pore. The structure combined with mutagenesis gives insight into the basis of calcium recognition.
钙转运在调节线粒体生理和病理生理学方面发挥着重要作用。线粒体钙单向转运蛋白（MCU）是一种钙选择性离子通道，是钙进入线粒体基质的主要介质。在这里，我们呈现了来自 至整体分辨率约 3.7 埃的全长 MCU 的冷冻电镜结构。我们的结构揭示了四聚体结构，其中可溶性和跨膜结构域在通道内采用不同的对称排列。MCU 孔道的保守 W-D-Φ-Φ-E-P-V-T-Y 序列基序形成一个选择性过滤器，由沿通道孔道中心轴隔开的两个酸性环组成。该结构与突变分析相结合，深入了解了钙识别的基础。
