Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters Journal Article


Authors: Baradaran, R.; Wang, C.; Siliciano, A. F.; Long, S. B.
Article Title: Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters
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 angstrom and 3.2 angstrom 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.
Keywords: antibodies; system; crystal-structure; essential component; membrane-proteins; potassium channel; ion-channel; k+ channel; ca2+ uptake; mcur1
Journal Title: Nature
Volume: 559
Issue: 7715
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2018-07-26
Start Page: 580
End Page: 584
Language: English
ACCESSION: WOS:000439850800049
DOI: 10.1038/s41586-018-0331-8
PROVIDER: wos
PUBMED: 29995857
Notes: Article -- Source: Wos
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MSK Authors
  1. Stephen Barstow Long
    20 Long
  2. Chongyuan Wang
    2 Wang