Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2

eLife

Rozbeh Baradaran¹  Chongyuan Wang²  Bryce D Delgado²  Agata Jacewicz²  Stephen Barstow Long² 

[1] Graduate Program in Biochemistry and Structural Biology, Cell and Developmental Biology, and Molecular Biology, Weill Cornell Medicine Graduate School of Medical Sciences, New York, United States;Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States;

关键词: tribolium castaneum;    ion channel;    calcium channel;    toxin;    gating;    membrane structure;   

DOI  :  10.7554/eLife.59991

来源: DOAJ

【 摘 要 】

The mitochondrial calcium uniporter is a Ca2+-gated ion channel complex that controls mitochondrial Ca2+ entry and regulates cell metabolism. MCU and EMRE form the channel while Ca2+-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 Ca2+ conditions. A Ca2+-bound structure of MICU1-MICU2 at 3.1 Å resolution indicates how Ca2+-dependent changes enable dynamic response to cytosolic Ca2+ signals.

【 授权许可】

Unknown