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- EMDB-22290: Structure of a mitochondrial calcium uniporter holocomplex (MICU1... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22290 | |||||||||
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Title | Structure of a mitochondrial calcium uniporter holocomplex (MICU1, MICU2, MCU, EMRE) in low Ca2+ | |||||||||
![]() | main map. Sharpened | |||||||||
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![]() | ion channel / calcium channel / mitochondrial calcium uniporter / MCU / EMRE / mitochondria / TRANSPORT PROTEIN-CALCIUM BINDING PROTEIN complex | |||||||||
Function / homology | ![]() mitochondrial crista junction / positive regulation of cristae formation / negative regulation of mitochondrial calcium ion concentration / regulation of cellular hyperosmotic salinity response / uniporter activity / Processing of SMDT1 / mitochondrial calcium ion transmembrane transport / uniplex complex / Mitochondrial calcium ion transport / positive regulation of mitochondrial calcium ion concentration ...mitochondrial crista junction / positive regulation of cristae formation / negative regulation of mitochondrial calcium ion concentration / regulation of cellular hyperosmotic salinity response / uniporter activity / Processing of SMDT1 / mitochondrial calcium ion transmembrane transport / uniplex complex / Mitochondrial calcium ion transport / positive regulation of mitochondrial calcium ion concentration / mitochondrial calcium ion homeostasis / calcium ion sensor activity / calcium import into the mitochondrion / calcium ion import / calcium channel inhibitor activity / calcium channel complex / Mitochondrial protein degradation / calcium channel activity / protein homooligomerization / mitochondrial membrane / mitochondrial intermembrane space / defense response / mitochondrial inner membrane / protein heterodimerization activity / calcium ion binding / mitochondrion / identical protein binding Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | Long SB / Wang C | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures reveal gatekeeping of the mitochondrial Ca uniporter by MICU1-MICU2. Authors: Chongyuan Wang / Agata Jacewicz / Bryce D Delgado / Rozbeh Baradaran / Stephen Barstow Long / ![]() 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 ...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. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 74.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 24 KB 24 KB | Display Display | ![]() |
Images | ![]() | 65.7 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 3 MB 2.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6xqnMC ![]() 6xqoC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | main map. Sharpened | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.064 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Additional map: sharpened map calculated from the first 6 frames.
File | emd_22290_additional_1.map | ||||||||||||
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Annotation | sharpened map calculated from the first 6 frames. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: unsharpened map
File | emd_22290_additional_2.map | ||||||||||||
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Annotation | unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Mitochondrial Calcium Uniporter holocomplex
Entire | Name: Mitochondrial Calcium Uniporter holocomplex |
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Components |
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-Supramolecule #1: Mitochondrial Calcium Uniporter holocomplex
Supramolecule | Name: Mitochondrial Calcium Uniporter holocomplex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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-Supramolecule #2: EMRE
Supramolecule | Name: EMRE / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #3: MCU
Supramolecule | Name: MCU / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: ![]() ![]() |
-Supramolecule #4: MICU1-MICU2 heterodimer
Supramolecule | Name: MICU1-MICU2 heterodimer / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3-#4 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Protein EMRE homolog, mitochondrial-like Protein
Macromolecule | Name: Protein EMRE homolog, mitochondrial-like Protein / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 7.37219 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GPTAAALETA VYSKSGGLLP EPHRTSFGII RLILTVVPGL LIGAAISKNI ANFLEENDLF VPSDDDDDDD UniProtKB: Essential MCU regulator, mitochondrial |
-Macromolecule #2: Calcium uniporter protein
Macromolecule | Name: Calcium uniporter protein / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 23.6341 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GPTAAALERL TTEEVQGLSD VKTLVNQLYE ALNVREHQLQ KEVELTTQLE TLQQELLPLE EKKLELEQVA NRRSNWMAWA GLGLMSVQF GILARLTWWE YSWDIMEPVT YFVTYGTAMA AYAYFVLTRE EYILNDVRDR QQLLLLHKKA KKTGFDVNQY N VLKDQIAK ...String: GPTAAALERL TTEEVQGLSD VKTLVNQLYE ALNVREHQLQ KEVELTTQLE TLQQELLPLE EKKLELEQVA NRRSNWMAWA GLGLMSVQF GILARLTWWE YSWDIMEPVT YFVTYGTAMA AYAYFVLTRE EYILNDVRDR QQLLLLHKKA KKTGFDVNQY N VLKDQIAK LELDLKRLRD PLKLRLPPKA AAKEEGGWSH PQFEK UniProtKB: Calcium uniporter protein, mitochondrial |
-Macromolecule #3: Calcium uptake protein 1, mitochondrial
Macromolecule | Name: Calcium uptake protein 1, mitochondrial / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 45.422883 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GPTAAALEPH PEEKKKKRSG FRDRKVMEYE NRIRAYSTPD KIFRYFATLK VISEPGEAEV FMTPEDFVRS ITPNEKQPEH LGLDQYIIK RFDGKKISQE REKFADEGSI FYTLGECGLI SFSDYIFLTT VLSTPQRNFE IAFKMFDLNG DGEVDMEEFE Q VQSIIRSQ ...String: GPTAAALEPH PEEKKKKRSG FRDRKVMEYE NRIRAYSTPD KIFRYFATLK VISEPGEAEV FMTPEDFVRS ITPNEKQPEH LGLDQYIIK RFDGKKISQE REKFADEGSI FYTLGECGLI SFSDYIFLTT VLSTPQRNFE IAFKMFDLNG DGEVDMEEFE Q VQSIIRSQ TSMGMRHRDR PTTGNTLKSG LCSALTTYFF GADLKGKLTI KNFLEFQRKL QHDVLKLEFE RHDPVDGRIT ER QFGGMLL AYSGVQSKKL TAMQRQLKKH FKEGKGLTFQ EVENFFTFLK NINDVDTALS FYHMAGASLD KVTMQQVART VAK VELSDH VCDVVFALFD CDGNGELSNK EFVSIMKQRL MRGLEKPKDM GFTRLMQAMW KCAQETAWDF ALPKQSNW UniProtKB: Calcium uptake protein 1, mitochondrial |
-Macromolecule #4: Calcium uptake protein 2, mitochondrial
Macromolecule | Name: Calcium uptake protein 2, mitochondrial / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 44.980609 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: HHSRVSVAAR DGSFTVSAQK NVEHGIIYIG KPSLRKQRFM QFSSLEHEGE YYMTPRDFLF SVMFEQMERK TSVKKLTKKD IEDTLSGIQ TAGCGSTFFR DLGDKGLISY TEYLFLLTIL TKPHSGFHVA FKMLDTDGNE MIEKREFFKL QKIISKQDDL M TVKTNETG ...String: HHSRVSVAAR DGSFTVSAQK NVEHGIIYIG KPSLRKQRFM QFSSLEHEGE YYMTPRDFLF SVMFEQMERK TSVKKLTKKD IEDTLSGIQ TAGCGSTFFR DLGDKGLISY TEYLFLLTIL TKPHSGFHVA FKMLDTDGNE MIEKREFFKL QKIISKQDDL M TVKTNETG YQEAIVKEPE INTTLQMRFF GKRGQRKLHY KEFRRFMENL QTEIQEMEFL QFSKGLSFMR KEDFAEWLLF FT NTENKDI YWKNVREKLS AGESISLDEF KSFCHFTTHL EDFAIAMQMF SLAHRPVRLA EFKRAVKVAT GQELSNNILD TVF KIFDLD GDECLSHEEF LGVLKNRMHR GLWVPQHQSI QEYWKCVKKE SIKGVKEVWK QAGKGLF UniProtKB: Calcium uptake protein 2, mitochondrial |
-Macromolecule #5: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 5 / Number of copies: 1 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.0 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 400 / Support film - Material: CARBON / Support film - topology: HOLEY ARRAY | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: 2 second blot, blot force of 0. | ||||||||||||
Details | Monodisperse sample |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Detector mode: SUPER-RESOLUTION / Digitization - Frames/image: 1-40 / Number grids imaged: 5 / Number real images: 21115 / Average exposure time: 4.0 sec. / Average electron dose: 71.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: -3.0 µm / Nominal defocus min: -1.0 µm / Nominal magnification: 22500 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 124 / Target criteria: Correlation coefficient |
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Output model | ![]() PDB-6xqn: |