Journal Article

Cryo-EM structure of a mitochondrial calcium uniporter

Wu, Mengyu, Herzik, Mark A., Lander, Gabriel C., Yin, Ying, Yoo, Jiho, Lee, Seok-Yong

2018

Overview

Maintaining the correct balance of calcium concentrations between the cytosol and the mitochondria is essential for cellular physiology. A calcium-selective channel called the mitochondrial calcium uniporter (MCU) mediates calcium entry into mitochondria. Yoo et al. report the high-resolution structure of MCU from Neurospora crassa. The channel is formed by four MCU protomers with differing symmetry between the soluble and membrane domains. The structure, together with mutagenesis, suggests that two acidic rings inside the channel provide the selectivity for calcium. Science , this issue p. 506 The structure of the mitochondrial calcium uniporter reveals a tetrameric architecture and the molecular framework underlying calcium selectivity. 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 Neurospora crassa 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.

• Publisher: The American Association for the Advancement of Science
• Subject: Amino Acid Motifs / Calcium / Calcium (mitochondrial) / Calcium - metabolism / Calcium Channels - chemistry / Calcium Channels - genetics / Calcium Channels - metabolism / Calcium Channels - ultrastructure / Calcium influx / Calcium transport / Conserved Sequence / Cryoelectron Microscopy / Cytosol / Electron microscopy / Fungal Proteins - chemistry / Fungal Proteins - genetics / Fungal Proteins - metabolism / Fungal Proteins - ultrastructure / Ion channels / Mitochondria / Models, Chemical / Mutagenesis / Neurospora / Neurospora crassa / Neurospora crassa - metabolism / Physiology / Protein Conformation / Protein Multimerization / Selectivity / Symmetry / Transmembrane domains