@article{9e7bf4c9fe5247e1907ef98c30756154,
title = "Cryo-EM structure of a fungal mitochondrial calcium uniporter",
abstract = "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 {\AA} 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.",
author = "Nguyen, {Nam X.} and Armache, {Jean Paul} and Changkeun Lee and Yi Yang and Weizhong Zeng and Mootha, {Vamsi K.} and Yifan Cheng and Bai, {Xiao chen} and Youxing Jiang",
note = "Funding Information: Acknowledgements We thank J. Guo and Q. Chen for technical assistance and manuscript preparation, and J. Frauenfeld (Salipro Biotech) for the recombinant saposin construct. Negative-stained EM data acquisition and sample optimization for cryo-EM were performed at the University of California San Francisco; we thank M. Braunfeld for supervision of the microscopes. Phase plate cryo-EM data were collected at the University of Texas Southwestern Medical Center Cryo-EM Facility, which is funded by the CPRIT Core Facility Support Award RP170644; we thank D. Nicastro and Z. Chen for technical support and facility access. This work was supported in part by the Howard Hughes Medical Institute (to Y.J., V.K.M. and Y.C.), the National Institutes of Health (grant GM079179 to Y.J.; grants R01GM098672, S10OD020054, and S10OD021741 to Y.C.), the Welch Foundation (Grant I-1578 to Y.J.), the Cancer Prevention and Research Initiative of Texas (to X.B.) and the Virginia Murchison Linthicum Scholar in Medical Research fund (to X.B.). Publisher Copyright: {\textcopyright} 2018, Macmillan Publishers Ltd., part of Springer Nature.",
year = "2018",
month = jul,
day = "26",
doi = "10.1038/s41586-018-0333-6",
language = "English (US)",
volume = "559",
pages = "570--574",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7715",
}