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- EMDB-21642: 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-21642 | |||||||||
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Title | Cryo-EM structure of mitochondrial calcium uniporter holocomplex in low Ca2+ | |||||||||
![]() | membrane protein | |||||||||
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Function / homology | ![]() 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 / calcium import into the mitochondrion / positive regulation of mitochondrial calcium ion concentration / mitochondrial calcium ion homeostasis ...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 / calcium import into the mitochondrion / positive regulation of mitochondrial calcium ion concentration / mitochondrial calcium ion homeostasis / calcium ion import / positive regulation of neutrophil chemotaxis / positive regulation of mitochondrial fission / Mitochondrial protein degradation / calcium channel complex / mitochondrial membrane / calcium-mediated signaling / calcium channel activity / protein homooligomerization / positive regulation of insulin secretion / mitochondrial intermembrane space / defense response / protein complex oligomerization / glucose homeostasis / mitochondrial inner membrane / mitochondrial matrix / protein heterodimerization activity / calcium ion binding / mitochondrion / nucleoplasm / identical protein binding Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Feng L / Zhang J / Fan M | |||||||||
![]() | ![]() 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) | ![]() ![]() | 13.8 KB 13.8 KB | Display Display | ![]() |
Images | ![]() | 44.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 437 KB | Display | ![]() |
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Full document | ![]() | 436.6 KB | Display | |
Data in XML | ![]() | 7 KB | Display | |
Data in CIF | ![]() | 8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6wdnMC ![]() 6wdoC 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: 1.06 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 uptake protein 2, mitochondrial, Calcium uptake protein 1...
Entire | Name: Calcium uptake protein 2, mitochondrial, Calcium uptake protein 1, mitochondrial, Essential MCU regulator, mitochondrial, Calcium uniporter protein, mitochondrial complex |
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Components |
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-Supramolecule #1: Calcium uptake protein 2, mitochondrial, Calcium uptake protein 1...
Supramolecule | Name: Calcium uptake protein 2, mitochondrial, Calcium uptake protein 1, mitochondrial, Essential MCU regulator, mitochondrial, Calcium uniporter protein, mitochondrial complex type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() |
-Macromolecule #1: Calcium uptake protein 2, mitochondrial
Macromolecule | Name: Calcium uptake protein 2, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.755582 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SLRKQRFMQF SSLEHEGEYY MTPRDFLFSV MFEQMERKTS VKKLTKKDIE DTLSGIQTAG CGSTFFRDLG DKGLISYTEY LFLLTILTK PHSGFHVAFK MLDTDGNEMI EKREFFKLQK IISKQDDLMT VKTNETGYQE AIVKEPEINT TLQMRFFGKR G QRKLHYKE ...String: SLRKQRFMQF SSLEHEGEYY MTPRDFLFSV MFEQMERKTS VKKLTKKDIE DTLSGIQTAG CGSTFFRDLG DKGLISYTEY LFLLTILTK PHSGFHVAFK MLDTDGNEMI EKREFFKLQK IISKQDDLMT VKTNETGYQE AIVKEPEINT TLQMRFFGKR G QRKLHYKE FRRFMENLQT EIQEMEFLQF SKGLSFMRKE DFAEWLLFFT NTENKDIYWK NVREKLSAGE SISLDEFKSF CH FTTHLED FAIAMQMFSL AHRPVRLAEF KRAVKVATGQ ELSNNILDTV FKIFDLDGDE CLSHEEFLGV LKNRMHRGLW VPQ HQSIQE YWKCVKKES |
-Macromolecule #2: Calcium uptake protein 1, mitochondrial
Macromolecule | Name: Calcium uptake protein 1, mitochondrial / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.900891 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 RLMRGLEKPK DMGFTRLMQA MWKCAQE |
-Macromolecule #3: Essential MCU regulator, mitochondrial
Macromolecule | Name: Essential MCU regulator, mitochondrial / type: protein_or_peptide / ID: 3 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 5.667833 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: VIVTRSGAIL PKPVKMSFGL LRVFSIVIPF LYVGTLISKN FAALLEEHDI F |
-Macromolecule #4: Calcium uniporter protein, mitochondrial
Macromolecule | Name: Calcium uniporter protein, mitochondrial / type: protein_or_peptide / ID: 4 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 21.256521 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: SHENAATLND VKTLVQQLYT TLCIEQHQLN KERELIERLE DLKEQLAPLE KVRIEISRKA EKRTTLVLWG GLAYMATQFG ILARLTWWE YSWDIMEPVT YFITYGSAMA MYAYFVMTRQ EYVYPEARDR QYLLFFHKGA KKSRFDLEKY NQLKDAIAQA E MDLKRLRD PLQVHLPLRQ |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
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 TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: SUPER-RESOLUTION / Average electron dose: 53.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 53216 |
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Initial angle assignment | Type: PROJECTION MATCHING |
Final angle assignment | Type: PROJECTION MATCHING |