Cryo-EM structure of a fungal mitochondrial calcium uniporter

Nam X. Nguyen, Jean Paul Armache, Changkeun Lee, Yi Yang, Weizhong Zeng, Vamsi K. Mootha, Yifan Cheng, Xiao chen Bai, Youxing Jiang

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)570-574
Number of pages5
JournalNature
Volume559
Issue number7715
DOIs
StatePublished - Jul 26 2018

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Fungal Structures
Neosartorya
Cryoelectron Microscopy
Mitochondrial Membranes
Calcium Channels
Aspartic Acid
Glutamic Acid
Fungi
Ions
Calcium
mitochondrial calcium uniporter

ASJC Scopus subject areas

  • General

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Nguyen, N. X., Armache, J. P., Lee, C., Yang, Y., Zeng, W., Mootha, V. K., ... Jiang, Y. (2018). Cryo-EM structure of a fungal mitochondrial calcium uniporter. Nature, 559(7715), 570-574. https://doi.org/10.1038/s41586-018-0333-6

Cryo-EM structure of a fungal mitochondrial calcium uniporter. / Nguyen, Nam X.; Armache, Jean Paul; Lee, Changkeun; Yang, Yi; Zeng, Weizhong; Mootha, Vamsi K.; Cheng, Yifan; Bai, Xiao chen; Jiang, Youxing.

In: Nature, Vol. 559, No. 7715, 26.07.2018, p. 570-574.

Research output: Contribution to journalArticle

Nguyen, NX, Armache, JP, Lee, C, Yang, Y, Zeng, W, Mootha, VK, Cheng, Y, Bai, XC & Jiang, Y 2018, 'Cryo-EM structure of a fungal mitochondrial calcium uniporter', Nature, vol. 559, no. 7715, pp. 570-574. https://doi.org/10.1038/s41586-018-0333-6
Nguyen NX, Armache JP, Lee C, Yang Y, Zeng W, Mootha VK et al. Cryo-EM structure of a fungal mitochondrial calcium uniporter. Nature. 2018 Jul 26;559(7715):570-574. https://doi.org/10.1038/s41586-018-0333-6
Nguyen, Nam X. ; Armache, Jean Paul ; Lee, Changkeun ; Yang, Yi ; Zeng, Weizhong ; Mootha, Vamsi K. ; Cheng, Yifan ; Bai, Xiao chen ; Jiang, Youxing. / Cryo-EM structure of a fungal mitochondrial calcium uniporter. In: Nature. 2018 ; Vol. 559, No. 7715. pp. 570-574.
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