6XQO

Structure of the human MICU1-MICU2 heterodimer, calcium bound, in association with a lipid nanodisc

Summary for 6XQO

• Entry DOI: 10.2210/pdb6xqo/pdb
• EMDB information: 22290 22291
• Descriptor: Calcium uptake protein 1, mitochondrial, Calcium uptake protein 2, mitochondrial, CALCIUM ION (3 entities in total)
• Functional Keywords: ion channel, calcium channel, mitochondrial calcium uniporter, mcu, emre, mitochondria, calcium binding protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 90563.80

Authors

Long, S.B.,Wang, C.,Baradaran, R.,Jacewicz, A.,Delgado, B. (deposition date: 2020-07-09, release date: 2020-07-29, Last modification date: 2024-03-06)

Primary citation

Wang, C.,Jacewicz, A.,Delgado, B.D.,Baradaran, R.,Long, S.B.
Structures reveal gatekeeping of the mitochondrial Ca 2+ uniporter by MICU1-MICU2.
Elife, 9:-, 2020

PubMed Abstract: 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.

PubMed: 32667285
DOI: 10.7554/eLife.59991

Experimental method

ELECTRON MICROSCOPY (3.1 Å)