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Cryo-EM structure of a fungal mitochondrial calcium uniporter

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...

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Bibliographic Details
Published in:Nature (London) 2018-07, Vol.559 (7715), p.570-574
Main Authors: Nguyen, Nam X., Armache, Jean-Paul, Lee, Changkeun, Yang, Yi, Zeng, Weizhong, Mootha, Vamsi K., Cheng, Yifan, Bai, Xiao-chen, Jiang, Youxing
Format: Article
Language:English
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Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-018-0333-6