Title | Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Baradaran R, Wang C, Siliciano AFrancis, Long SBarstow |
Journal | Nature |
Volume | 559 |
Issue | 7715 |
Pagination | 580-584 |
Date Published | 2018 07 |
ISSN | 1476-4687 |
Keywords | Animals, Caenorhabditis elegans, Calcium, Calcium Channels, Cryoelectron Microscopy, Ion Channel Gating, Models, Molecular, Phialophora, Protein Multimerization, Protein Subunits, Zebrafish |
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. |
DOI | 10.1038/s41586-018-0331-8 |
Alternate Journal | Nature |
PubMed ID | 29995857 |
PubMed Central ID | PMC6336196 |
Grant List | P30 CA008748 / CA / NCI NIH HHS / United States R01 GM094273 / GM / NIGMS NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |
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