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Yorodumi- EMDB-21642: Cryo-EM structure of mitochondrial calcium uniporter holocomplex ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-21642 | |||||||||
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Title | Cryo-EM structure of mitochondrial calcium uniporter holocomplex in low Ca2+ | |||||||||
Map data | membrane protein | |||||||||
Sample |
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Function / homology | Function and homology information 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 / calcium import into the mitochondrion / Mitochondrial calcium ion transport / 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 / calcium import into the mitochondrion / Mitochondrial calcium ion transport / positive regulation of mitochondrial calcium ion concentration / mitochondrial calcium ion homeostasis / calcium ion import / positive regulation of neutrophil chemotaxis / positive regulation of mitochondrial fission / calcium channel complex / calcium-mediated signaling / mitochondrial membrane / calcium channel activity / protein homooligomerization / defense response / mitochondrial intermembrane space / positive regulation of insulin secretion / glucose homeostasis / protein complex oligomerization / mitochondrial inner membrane / mitochondrial matrix / protein heterodimerization activity / calcium ion binding / mitochondrion / nucleoplasm / identical protein binding Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Feng L / Zhang J / Fan M | |||||||||
Citation | Journal: Nature / Year: 2020 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 |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_21642.map.gz | 168 MB | EMDB map data format | |
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Header (meta data) | emd-21642-v30.xml emd-21642.xml | 13.8 KB 13.8 KB | Display Display | EMDB header |
Images | emd_21642.png | 44.7 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-21642 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-21642 | HTTPS FTP |
-Related structure data
Related structure data | 6wdnMC 6wdoC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_21642.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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
-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: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 39.755582 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 41.900891 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 5.667833 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 21.256521 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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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Processing | single particle reconstruction |
Aggregation state | particle |
-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 |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm |
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: 53.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Initial angle assignment | Type: PROJECTION MATCHING |
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Final angle assignment | Type: PROJECTION MATCHING |
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 |