National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM131921
米国
National Institutes of Health/National Cancer Institute (NIH/NCI)
P30CA008748
米国
引用
ジャーナル: J Mol Biol / 年: 2020 タイトル: Structure and Reconstitution of an MCU-EMRE Mitochondrial Ca Uniporter Complex. 著者: Chongyuan Wang / Rozbeh Baradaran / Stephen Barstow Long / 要旨: The proteins MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans, a highly selective and tightly controlled Ca channel of the inner mitochondrial ...The proteins MCU and EMRE form the minimal functional unit of the mitochondrial calcium uniporter complex in metazoans, a highly selective and tightly controlled Ca 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 Ca 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.