Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59991 |
| _version_ | 1811181118696718336 |
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| author | Chongyuan Wang Agata Jacewicz Bryce D Delgado Rozbeh Baradaran Stephen Barstow Long |
| author_facet | Chongyuan Wang Agata Jacewicz Bryce D Delgado Rozbeh Baradaran Stephen Barstow Long |
| author_sort | Chongyuan Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:14:14Z |
| format | Article |
| id | doaj.art-babbf9f640f54b3e8fb3f9f3f6888c17 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:14:14Z |
| publishDate | 2020-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-babbf9f640f54b3e8fb3f9f3f6888c172022-12-22T04:32:25ZengeLife Sciences Publications LtdeLife2050-084X2020-07-01910.7554/eLife.59991Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2Chongyuan Wang0Agata Jacewicz1Bryce D Delgado2Rozbeh Baradaran3Stephen Barstow Long4https://orcid.org/0000-0002-8144-1398Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States; 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 StatesStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesStructural Biology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesThe 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.https://elifesciences.org/articles/59991tribolium castaneumion channelcalcium channeltoxingatingmembrane structure |
| spellingShingle | Chongyuan Wang Agata Jacewicz Bryce D Delgado Rozbeh Baradaran Stephen Barstow Long Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 eLife tribolium castaneum ion channel calcium channel toxin gating membrane structure |
| title | Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 |
| title_full | Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 |
| title_fullStr | Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 |
| title_full_unstemmed | Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 |
| title_short | Structures reveal gatekeeping of the mitochondrial Ca2+ uniporter by MICU1-MICU2 |
| title_sort | structures reveal gatekeeping of the mitochondrial ca2 uniporter by micu1 micu2 |
| topic | tribolium castaneum ion channel calcium channel toxin gating membrane structure |
| url | https://elifesciences.org/articles/59991 |
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