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: Elife / 年: 2020 タイトル: Structures reveal gatekeeping of the mitochondrial Ca uniporter by MICU1-MICU2. 著者: Chongyuan Wang / Agata Jacewicz / Bryce D Delgado / Rozbeh Baradaran / Stephen Barstow Long / 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.