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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-22215 | |||||||||
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Title | MCU holocomplex in High-calcium state | |||||||||
![]() | MCU holocomplex in High-calcium state | |||||||||
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![]() | ion channel / TRANSPORT PROTEIN | |||||||||
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 / channel activator activity / calcium import into the mitochondrion / calcium ion import / positive regulation of neutrophil chemotaxis / positive regulation of mitochondrial fission / calcium channel inhibitor activity / calcium channel complex / Mitochondrial protein degradation / calcium-mediated signaling / calcium channel activity / protein homooligomerization / positive regulation of insulin secretion / mitochondrial membrane / mitochondrial intermembrane space / defense response / glucose homeostasis / protein complex oligomerization / protein-macromolecule adaptor activity / 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: 4.17 Å | |||||||||
![]() | Wang Y / Jiang Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into the Ca-dependent gating of the human mitochondrial calcium uniporter. Authors: Yan Wang / Yan Han / Ji She / Nam X Nguyen / Vamsi K Mootha / Xiao-Chen Bai / Youxing Jiang / ![]() Abstract: Mitochondrial Ca uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, ...Mitochondrial Ca uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca-dependent manner. Here, we present the EM structures of the human mitochondrial calcium uniporter holocomplex (uniplex) in the presence and absence of Ca, revealing distinct Ca dependent assembly of the uniplex. Our structural observations suggest that Ca changes the dimerization interaction between MICU1 and MICU2, which in turn determines how the MICU1-MICU2 subcomplex interacts with the MCU-EMRE channel and, consequently, changes the distribution of the uniplex assemblies between the blocked and unblocked states. | |||||||||
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 | ![]() | 166.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.2 KB 14.2 KB | Display Display | ![]() |
Images | ![]() | 37.2 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6xjvMC ![]() 6xjxC 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 | MCU holocomplex in High-calcium state | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.833 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 : MCU/EMRE/MICU1/MICU2 complex
Entire | Name: MCU/EMRE/MICU1/MICU2 complex |
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Components |
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-Supramolecule #1: MCU/EMRE/MICU1/MICU2 complex
Supramolecule | Name: MCU/EMRE/MICU1/MICU2 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all / Details: high calcium state |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 529 KDa |
-Macromolecule #1: Calcium uniporter protein, mitochondrial
Macromolecule | Name: Calcium uniporter protein, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 8 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.920828 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MAAAAGRSLL LLLSSRGGGG GGAGGCGALT AGCFPGLGVS RHRQQQHHRT VHQRIASWQN LGAVYCSTVV PSDDVTVVYQ NGLPVISVR LPSRRERCQF TLKPISDSVG VFLRQLQEED RGIDRVAIYS PDGVRVAAST GIDLLLLDDF KLVINDLTYH V RPPKRDLL ...String: MAAAAGRSLL LLLSSRGGGG GGAGGCGALT AGCFPGLGVS RHRQQQHHRT VHQRIASWQN LGAVYCSTVV PSDDVTVVYQ NGLPVISVR LPSRRERCQF TLKPISDSVG VFLRQLQEED RGIDRVAIYS PDGVRVAAST GIDLLLLDDF KLVINDLTYH V RPPKRDLL SHENAATLND VKTLVQQLYT TLCIEQHQLN KERELIERLE DLKEQLAPLE KVRIEISRKA EKRTTLVLWG GL AYMATQF GILARLTWWE YSWDIMEPVT YFITYGSAMA MYAYFVMTRQ EYVYPEARDR QYLLFFHKGA KKSRFDLEKY NQL KDAIAQ AEMDLKRLRD PLQVHLPLRQ IGEKD 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: 11.45414 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASGAARWLV LAPVRSGALR SGPSLRKDGD VSAAWSGSGR SLVPSRSVIV TRSGAILPKP VKMSFGLLRV FSIVIPFLYV GTLISKNFA ALLEEHDIFV PEDDDDDD UniProtKB: Essential MCU regulator, mitochondrial |
-Macromolecule #3: Calcium uptake protein 1, mitochondrial
Macromolecule | Name: Calcium uptake protein 1, mitochondrial / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 54.432258 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MFRLNSLSAL AELAVGSRWY HGGSQPIQIR RRLMMVAFLG ASAVTASTGL LWKRAHAESP PCVDNLKSDI GDKGKNKDEG DVCNHEKKT ADLAPHPEEK KKKRSGFRDR KVMEYENRIR AYSTPDKIFR YFATLKVISE PGEAEVFMTP EDFVRSITPN E KQPEHLGL ...String: MFRLNSLSAL AELAVGSRWY HGGSQPIQIR RRLMMVAFLG ASAVTASTGL LWKRAHAESP PCVDNLKSDI GDKGKNKDEG DVCNHEKKT ADLAPHPEEK KKKRSGFRDR KVMEYENRIR AYSTPDKIFR YFATLKVISE PGEAEVFMTP EDFVRSITPN E KQPEHLGL DQYIIKRFDG KKISQEREKF ADEGSIFYTL GECGLISFSD YIFLTTVLST PQRNFEIAFK MFDLNGDGEV DM EEFEQVQ SIIRSQTSMG MRHRDRPTTG NTLKSGLCSA LTTYFFGADL KGKLTIKNFL EFQRKLQHDV LKLEFERHDP VDG RITERQ FGGMLLAYSG VQSKKLTAMQ RQLKKHFKEG KGLTFQEVEN FFTFLKNIND VDTALSFYHM AGASLDKVTM QQVA RTVAK VELSDHVCDV VFALFDCDGN GELSNKEFVS IMKQRLMRGL EKPKDMGFTR LMQAMWKCAQ ETAWDFALPK Q 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: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 49.742141 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MAAAAGSCAR VAAWGGKLRR GLAVSRQAVR SPGPLAAAVA GAALAGAGAA WHHSRVSVAA RDGSFTVSAQ KNVEHGIIYI GKPSLRKQR FMQFSSLEHE GEYYMTPRDF LFSVMFEQME RKTSVKKLTK KDIEDTLSGI QTAGCGSTFF RDLGDKGLIS Y TEYLFLLT ...String: MAAAAGSCAR VAAWGGKLRR GLAVSRQAVR SPGPLAAAVA GAALAGAGAA WHHSRVSVAA RDGSFTVSAQ KNVEHGIIYI GKPSLRKQR FMQFSSLEHE GEYYMTPRDF LFSVMFEQME RKTSVKKLTK KDIEDTLSGI QTAGCGSTFF RDLGDKGLIS Y TEYLFLLT ILTKPHSGFH VAFKMLDTDG NEMIEKREFF KLQKIISKQD DLMTVKTNET GYQEAIVKEP EINTTLQMRF FG KRGQRKL HYKEFRRFME NLQTEIQEME FLQFSKGLSF MRKEDFAEWL LFFTNTENKD IYWKNVREKL SAGESISLDE FKS FCHFTT HLEDFAIAMQ MFSLAHRPVR LAEFKRAVKV ATGQELSNNI LDTVFKIFDL DGDECLSHEE FLGVLKNRMH RGLW VPQHQ SIQEYWKCVK KESIKGVKEV WKQAGKGLF UniProtKB: Calcium uptake protein 2, mitochondrial |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.3 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: blot for 4 seconds before plunging. |
Details | This sample was reconstituted in Msp1 nanodiscs |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 2.0 sec. / Average electron dose: 30.9 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 70.0 µm / Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: EMDB MAP EMDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 4.17 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 19924 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |