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Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters

Author

Listed:
  • Rozbeh Baradaran

    (Memorial Sloan Kettering Cancer Center)

  • Chongyuan Wang

    (Memorial Sloan Kettering Cancer Center)

  • Andrew Francis Siliciano

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program)

  • Stephen Barstow Long

    (Memorial Sloan Kettering Cancer Center)

Abstract

The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Å and 3.2 Å resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers. The atomic model of C. europaea MCU shows that a conserved WDXXEP signature sequence forms the selectivity filter, in which calcium ions are arranged in single file. Coiled-coil legs connect the pore to N-terminal domains in the mitochondrial matrix. In C. europaea MCU, the N-terminal domains assemble as a dimer of dimers; in zebrafish MCU, they form an asymmetric crescent. The structures define principles that underlie ion permeation and calcium selectivity in this unusual channel.

Suggested Citation

  • Rozbeh Baradaran & Chongyuan Wang & Andrew Francis Siliciano & Stephen Barstow Long, 2018. "Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters," Nature, Nature, vol. 559(7715), pages 580-584, July.
    • Handle: RePEc:nat:nature:v:559:y:2018:i:7715:d:10.1038_s41586-018-0331-8
    DOI: 10.1038/s41586-018-0331-8
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    Cited by:

    1. Enrique Balderas & David R. Eberhardt & Sandra Lee & John M. Pleinis & Salah Sommakia & Anthony M. Balynas & Xue Yin & Mitchell C. Parker & Colin T. Maguire & Scott Cho & Marta W. Szulik & Anna Bakhti, 2022. "Mitochondrial calcium uniporter stabilization preserves energetic homeostasis during Complex I impairment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Zhihui He & Yonghui Zhao & Michael J. Rau & James A. J. Fitzpatrick & Rajan Sah & Hongzhen Hu & Peng Yuan, 2023. "Structural and functional analysis of human pannexin 2 channel," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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