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- EMDB-21643: Cryo-EM structure of mitochondrial calcium uniporter holocomplex ... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-21643 | |||||||||
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Title | Cryo-EM structure of mitochondrial calcium uniporter holocomplex in high Ca2+ | |||||||||
![]() | membrane protein![]() | |||||||||
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Function / homology | ![]() negative regulation of mitochondrial calcium ion concentration / regulation of cellular hyperosmotic salinity response / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Feng L / Zhang J | |||||||||
![]() | ![]() Title: Structure and mechanism of the mitochondrial Ca uniporter holocomplex. Authors: Minrui Fan / Jinru Zhang / Chen-Wei Tsai / Benjamin J Orlando / Madison Rodriguez / Yan Xu / Maofu Liao / Ming-Feng Tsai / Liang Feng / ![]() Abstract: Mitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains ...Mitochondria take up Ca through the mitochondrial calcium uniporter complex to regulate energy production, cytosolic Ca signalling and cell death. In mammals, the uniporter complex (uniplex) contains four core components: the pore-forming MCU protein, the gatekeepers MICU1 and MICU2, and an auxiliary subunit, EMRE, essential for Ca transport. To prevent detrimental Ca overload, the activity of MCU must be tightly regulated by MICUs, which sense changes in cytosolic Ca concentrations to switch MCU on and off. Here we report cryo-electron microscopic structures of the human mitochondrial calcium uniporter holocomplex in inhibited and Ca-activated states. These structures define the architecture of this multicomponent Ca-uptake machinery and reveal the gating mechanism by which MICUs control uniporter activity. Our work provides a framework for understanding regulated Ca uptake in mitochondria, and could suggest ways of modulating uniporter activity to treat diseases related to mitochondrial Ca overload. | |||||||||
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 | ![]() | 168 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.4 KB 15.4 KB | Display Display | ![]() |
Images | ![]() | 82.8 KB | ||
Filedesc metadata | ![]() | 6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wdoMC ![]() 6wdnC M: atomic model generated by this map C: citing same article ( |
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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 | membrane protein | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.1 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Calcium uniporter protein, mitochondrial, Essential MCU regulator...
Entire | Name: Calcium uniporter protein, mitochondrial, Essential MCU regulator, mitochondrial, Calcium uptake protein 1, mitochondrial, Calcium uptake protein 2, mitochondrial complex |
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Components |
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-Supramolecule #1: Calcium uniporter protein, mitochondrial, Essential MCU regulator...
Supramolecule | Name: Calcium uniporter protein, mitochondrial, Essential MCU regulator, mitochondrial, Calcium uptake protein 1, mitochondrial, Calcium uptake protein 2, mitochondrial complex type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Calcium uniporter protein, mitochondrial
Macromolecule | Name: Calcium uniporter protein, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 32.014904 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DVTVVYQNGL PVISVRLPSR RERCQFTLKP ISDSVGVFLR QLQEEDRGID RVAIYSPDGV RVAASTGIDL LLLDDFKLVI NDLTYHVRP PKRDLLSHEN AATLNDVKTL VQQLYTTLCI EQHQLNKERE LIERLEDLKE QLAPLEKVRI EISRKAEKRT T LVLWGGLA ...String: DVTVVYQNGL PVISVRLPSR RERCQFTLKP ISDSVGVFLR QLQEEDRGID RVAIYSPDGV RVAASTGIDL LLLDDFKLVI NDLTYHVRP PKRDLLSHEN AATLNDVKTL VQQLYTTLCI EQHQLNKERE LIERLEDLKE QLAPLEKVRI EISRKAEKRT T LVLWGGLA YMATQFGILA RLTWWEYSWD IMEPVTYFIT YGSAMAMYAY FVMTRQEYVY PEARDRQYLL FFHKGAKKSR FD LEKYNQL KDAIAQAEMD LKRLRDPLQV HLPLRQ UniProtKB: Calcium uniporter protein, mitochondrial |
-Macromolecule #2: Essential MCU regulator, mitochondrial
Macromolecule | Name: Essential MCU regulator, mitochondrial / type: protein_or_peptide / ID: 2 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 5.864078 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: VIVTRSGAIL PKPVKMSFGL LRVFSIVIPF LYVGTLISKN FAALLEEHDI FVP UniProtKB: Essential MCU regulator, mitochondrial |
-Macromolecule #3: Calcium uniporter protein, mitochondrial
Macromolecule | Name: Calcium uniporter protein, mitochondrial / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 31.406152 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DVTVVYQNGL PVISVRLPSR RERCQFTLKP ISDSVGVFLR QLQEEDRGID RVAIYSPDGV RVAASTGIDL LLLDDFKLVI NDLTYHVRP PKRDLLSHEN AATLNDVKTL VQQLYTTLCI EQHQLNKERE LIERLEDLKE QLAPLEKVRI EISRKAEKRT T LVLWGGLA ...String: DVTVVYQNGL PVISVRLPSR RERCQFTLKP ISDSVGVFLR QLQEEDRGID RVAIYSPDGV RVAASTGIDL LLLDDFKLVI NDLTYHVRP PKRDLLSHEN AATLNDVKTL VQQLYTTLCI EQHQLNKERE LIERLEDLKE QLAPLEKVRI EISRKAEKRT T LVLWGGLA YMATQFGILA RLTWWEYSWD IMEPVTYFIT YGSAMAMYAY FVMTRQEYVY PEARDRQYLL FFHKGAKKSR FD LEKYNQL KDAIAQAEMD LKRLRDPLQV H UniProtKB: Calcium uniporter protein, mitochondrial |
-Macromolecule #4: Calcium uptake protein 1, mitochondrial
Macromolecule | Name: Calcium uptake protein 1, mitochondrial / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 39.058488 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SGFRDRKVME YENRIRAYST PDKIFRYFAT LKVISEPGEA EVFMTPEDFV RSITPNEKQP EHLGLDQYII KRFDGKKISQ EREKFADEG SIFYTLGECG LISFSDYIFL TTVLSTPQRN FEIAFKMFDL NGDGEVDMEE FEQVQSIIRS QTSMGMRHRD R PTTGNTLK ...String: SGFRDRKVME YENRIRAYST PDKIFRYFAT LKVISEPGEA EVFMTPEDFV RSITPNEKQP EHLGLDQYII KRFDGKKISQ EREKFADEG SIFYTLGECG LISFSDYIFL TTVLSTPQRN FEIAFKMFDL NGDGEVDMEE FEQVQSIIRS QTSMGMRHRD R PTTGNTLK SGLCSALTTY FFGADLKGKL TIKNFLEFQR KLQHDVLKLE FERHDPVDGR ITERQFGGML LAYSGVQSKK LT AMQRQLK KHFKEGKGLT FQEVENFFTF LKNINDVDTA LSFYHMAGAS LDKVTMQQVA RTVAKVELSD HVCDVVFALF DCD GNGELS NKEFVSIMKQ RLM UniProtKB: Calcium uptake protein 1, mitochondrial |
-Macromolecule #5: Calcium uptake protein 2, mitochondrial
Macromolecule | Name: Calcium uptake protein 2, mitochondrial / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 36.682039 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: LRKQRFMQFS SLEHEGEYYM TPRDFLFSVM FEQMERKTSV KKLTKKDIED TLSGIQTAGC GSTFFRDLGD KGLISYTEYL FLLTILTKP HSGFHVAFKM LDTDGNEMIE KREFFKLQKI ISKQDDLMTV KTNETGYQEA IVKEPEINTT LQMRFFGKRG Q RKLHYKEF ...String: LRKQRFMQFS SLEHEGEYYM TPRDFLFSVM FEQMERKTSV KKLTKKDIED TLSGIQTAGC GSTFFRDLGD KGLISYTEYL FLLTILTKP HSGFHVAFKM LDTDGNEMIE KREFFKLQKI ISKQDDLMTV KTNETGYQEA IVKEPEINTT LQMRFFGKRG Q RKLHYKEF RRFMENLQTE IQEMEFLQFS KGLSFMRKED FAEWLLFFTN TENKDIYWKN VREKLSAGES ISLDEFKSFC HF TTHLEDF AIAMQMFSLA HRPVRLAEFK RAVKVATGQE LSNNILDTVF KIFDLDGDEC LSHEEFLGVL KNR UniProtKB: Calcium uptake protein 2, mitochondrial |
-Macromolecule #6: CALCIUM ION
Macromolecule | Name: CALCIUM ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: CA |
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Molecular weight | Theoretical: 40.078 Da |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 7.9 mg/mL |
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Buffer | pH: 7.4 |
Grid | Model: Quantifoil R2/1 / Material: GOLD / Support film - Material: CARBON / Support film - topology: HOLEY |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 30.0 e/Å2 |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |
Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic![]() |