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-Structure paper
タイトル | Structures reveal gatekeeping of the mitochondrial Ca uniporter by MICU1-MICU2. |
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ジャーナル・号・ページ | Elife, Vol. 9, Year 2020 |
掲載日 | 2020年7月15日 |
著者 | Chongyuan Wang / Agata Jacewicz / Bryce D Delgado / Rozbeh Baradaran / Stephen Barstow Long / |
PubMed 要旨 | The mitochondrial calcium uniporter is a Ca-gated ion channel complex that controls mitochondrial Ca entry and regulates cell metabolism. MCU and EMRE form the channel while Ca-dependent regulation ...The mitochondrial calcium uniporter is a Ca-gated ion channel complex that controls mitochondrial Ca entry and regulates cell metabolism. MCU and EMRE form the channel while Ca-dependent regulation is conferred by MICU1 and MICU2 through an enigmatic process. We present a cryo-EM structure of an MCU-EMRE-MICU1-MICU2 holocomplex comprising MCU and EMRE subunits from the beetle Tribolium castaneum in complex with a human MICU1-MICU2 heterodimer at 3.3 Å resolution. With analogy to how neuronal channels are blocked by protein toxins, a uniporter interaction domain on MICU1 binds to a channel receptor site comprising MCU and EMRE subunits to inhibit ion flow under resting Ca conditions. A Ca-bound structure of MICU1-MICU2 at 3.1 Å resolution indicates how Ca-dependent changes enable dynamic response to cytosolic Ca signals. |
リンク | Elife / PubMed:32667285 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.1 - 3.3 Å |
構造データ | EMDB-22290, PDB-6xqn: EMDB-22291, PDB-6xqo: |
化合物 | ChemComp-CA: |
由来 |
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キーワード | TRANSPORT PROTEIN/CALCIUM BINDING PROTEIN / ion channel / calcium channel / mitochondrial calcium uniporter / MCU / EMRE / mitochondria / TRANSPORT PROTEIN-CALCIUM BINDING PROTEIN complex / CALCIUM BINDING PROTEIN |