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-Structure paper
タイトル | Structure and mechanism of the mitochondrial Ca uniporter holocomplex. |
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ジャーナル・号・ページ | Nature, Vol. 582, Issue 7810, Page 129-133, Year 2020 |
掲載日 | 2020年5月20日 |
著者 | Minrui Fan / Jinru Zhang / Chen-Wei Tsai / Benjamin J Orlando / Madison Rodriguez / Yan Xu / Maofu Liao / Ming-Feng Tsai / Liang Feng / |
PubMed 要旨 | Mitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains ...Mitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca transport. To prevent detrimental Ca overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca concentrations to switch MCU on and off. Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca-activated states. These structures define the architecture of this multicomponent Ca-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca overload. |
リンク | Nature / PubMed:32494073 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 3.6 Å |
構造データ | EMDB-21642, PDB-6wdn: EMDB-21643, PDB-6wdo: |
化合物 | ChemComp-CA: |
由来 |
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キーワード | MEMBRANE PROTEIN |