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
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089708600&doi=10.7554%2feLife.59991&partnerID=40&md5=0bd1080cc13ba05ca72f7a4d492e0d3e
Notes:	Article -- Export Date: 1 September 2020 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/169768