Structure and reconstitution of an MCU–EMRE mitochondrial Ca(2+) uniporter complex Journal Article
| Authors: | Wang, C.; Baradaran, R.; Long, S. B. |
| Article Title: | Structure and reconstitution of an MCU–EMRE mitochondrial Ca(2+) uniporter complex |
| Abstract: | The proteins MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans, a highly selective and tightly controlled Ca2+ channel of the inner mitochondrial membrane that regulates cellular metabolism. Here we present functional reconstitution of an MCU–EMRE complex from the red flour beetle, Tribolium castaneum, and a cryo-EM structure of the complex at 3.5 Å resolution. Using a novel assay, we demonstrate robust Ca2+ uptake into proteoliposomes containing the purified complex. Uptake is dependent on EMRE and also on the mitochondrial lipid cardiolipin. The structure reveals a tetrameric channel with a single ion pore. EMRE is located at the periphery of the transmembrane domain and associates primarily with the first transmembrane helix of MCU. Coiled-coil and juxtamembrane domains within the matrix portion of the complex adopt markedly different conformations than in a structure of a human MCU–EMRE complex, suggesting that the structures represent different conformations of these functionally similar metazoan channels. © 2020 Elsevier Ltd |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; protein conformation; protein domain; protein localization; animal cell; protein purification; membrane protein; protein structure; mitochondrial membrane; cell metabolism; mitochondrion; reconstitution; cryoelectron microscopy; calcium transport; calcium ion; ion channel; calcium channel; priority journal; article; proteoliposome; cardiolipin; tribolium castaneum; flux assay; emre protein; mcu protein |
| Journal Title: | Journal of Molecular Biology |
| Volume: | 432 |
| Issue: | 20 |
| ISSN: | 0022-2836 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 2020-09-18 |
| Start Page: | 5632 |
| End Page: | 5648 |
| Language: | English |
| DOI: | 10.1016/j.jmb.2020.08.013 |
| PUBMED: | 32841658 |
| PROVIDER: | scopus |
| PMCID: | PMC7577567 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 November 2020 -- Source: Scopus |
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