Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2 Journal Article

Authors: Wang, C.; Jacewicz, A.; Delgado, B. D.; Baradaran, R.; Long, S. B.
Article Title: Structures reveal gatekeeping of the mitochondrial Ca(2+) uniporter by MICU1-MICU2
Abstract: 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. © 2020, Wang et al.
Keywords: biochemistry; molecular biophysics; membrane structure; chemical biology; ion channel; toxin; structural biology; gating; calcium channel; human; tribolium castaneum
Journal Title: eLife
Volume: 9
ISSN: 2050-084X
Publisher: eLife Sciences Publications Ltd.  
Date Published: 2020-07-15
Start Page: e59991
Language: English
DOI: 10.7554/eLife.59991
PUBMED: 32667285
PROVIDER: scopus
PMCID: PMC7434445
Notes: Article -- Export Date: 1 September 2020 -- Source: Scopus
Citation Impact
MSK Authors
  1. Stephen Barstow Long
    32 Long
  2. Chongyuan Wang
    6 Wang