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Cryo-EM structure of a fungal mitochondrial calcium uniporter

Author

Listed:
  • Nam X. Nguyen

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Jean-Paul Armache

    (University of California San Francisco)

  • Changkeun Lee

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    Amgen Discovery Research)

  • Yi Yang

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Weizhong Zeng

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Vamsi K. Mootha

    (Broad Institute)

  • Yifan Cheng

    (University of California San Francisco)

  • Xiao-chen Bai

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Youxing Jiang

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

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.

Suggested Citation

  • Nam X. Nguyen & Jean-Paul Armache & Changkeun Lee & Yi Yang & Weizhong Zeng & Vamsi K. Mootha & Yifan Cheng & Xiao-chen Bai & Youxing Jiang, 2018. "Cryo-EM structure of a fungal mitochondrial calcium uniporter," Nature, Nature, vol. 559(7715), pages 570-574, July.
    • Handle: RePEc:nat:nature:v:559:y:2018:i:7715:d:10.1038_s41586-018-0333-6
    DOI: 10.1038/s41586-018-0333-6
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