[English] 日本語
Yorodumi
- PDB-6xqn: Structure of a mitochondrial calcium uniporter holocomplex (MICU1... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6xqn
TitleStructure of a mitochondrial calcium uniporter holocomplex (MICU1, MICU2, MCU, EMRE) in low Ca2+
Components
  • Calcium uniporter protein
  • Calcium uptake protein 1, mitochondrial
  • Calcium uptake protein 2, mitochondrial
  • Protein EMRE homolog, mitochondrial-like Protein
KeywordsTRANSPORT PROTEIN/CALCIUM BINDING PROTEIN / ion channel / calcium channel / mitochondrial calcium uniporter / MCU / EMRE / mitochondria / TRANSPORT PROTEIN-CALCIUM BINDING PROTEIN complex
Function / homology
Function and homology information


regulation of cellular hyperosmotic salinity response / negative regulation of mitochondrial calcium ion concentration / Processing of SMDT1 / intracellular anatomical structure / mitochondrial calcium ion transmembrane transport / uniplex complex / Mitochondrial calcium ion transport / calcium import into the mitochondrion / positive regulation of mitochondrial calcium ion concentration / uniporter activity ...regulation of cellular hyperosmotic salinity response / negative regulation of mitochondrial calcium ion concentration / Processing of SMDT1 / intracellular anatomical structure / mitochondrial calcium ion transmembrane transport / uniplex complex / Mitochondrial calcium ion transport / calcium import into the mitochondrion / positive regulation of mitochondrial calcium ion concentration / uniporter activity / mitochondrial calcium ion homeostasis / integral component of mitochondrial membrane / integral component of mitochondrial inner membrane / calcium ion import / calcium channel complex / calcium channel activity / mitochondrial intermembrane space / protein homooligomerization / defense response / mitochondrial inner membrane / protein heterodimerization activity / calcium ion binding / mitochondrion / identical protein binding
Similarity search - Function
Essential MCU regulator, mitochondrial / Putative mitochondrial precursor protein / Calcium uptake protein 1/2/3 / Calcium uniporter protein, C-terminal / MCU family / Mitochondrial calcium uniporter / EF hand / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site ...Essential MCU regulator, mitochondrial / Putative mitochondrial precursor protein / Calcium uptake protein 1/2/3 / Calcium uniporter protein, C-terminal / MCU family / Mitochondrial calcium uniporter / EF hand / EF-hand domain pair / EF-hand, calcium binding motif / EF-Hand 1, calcium-binding site / EF-hand calcium-binding domain. / EF-hand calcium-binding domain profile. / EF-hand domain / EF-hand domain pair
Similarity search - Domain/homology
Calcium uniporter protein / Essential MCU regulator, mitochondrial / Calcium uptake protein 2, mitochondrial / Calcium uptake protein 1, mitochondrial
Similarity search - Component
Biological speciesTribolium castaneum (red flour beetle)
Homo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsLong, S.B. / Wang, C. / Baradaran, R. / Jacewicz, A. / Delgado, B.
Funding support United States, 2items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM131921 United States
National Institutes of Health/National Cancer Institute (NIH/NCI)P30CA008748 United States
CitationJournal: Elife / Year: 2020
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
DepositionJul 9, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 29, 2020Provider: repository / Type: Initial release
Revision 1.1Aug 5, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.pdbx_database_id_PubMed ..._citation.journal_volume / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Sep 30, 2020Group: Database references / Category: citation / citation_author / Item: _citation.title / _citation_author.identifier_ORCID

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Simplified surface model + fitted atomic model
  • EMDB-22290
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-22290
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
E: Protein EMRE homolog, mitochondrial-like Protein
A: Calcium uniporter protein
B: Calcium uniporter protein
G: Protein EMRE homolog, mitochondrial-like Protein
C: Calcium uniporter protein
H: Protein EMRE homolog, mitochondrial-like Protein
D: Calcium uniporter protein
I: Calcium uptake protein 1, mitochondrial
J: Calcium uptake protein 2, mitochondrial
hetero molecules


Theoretical massNumber of molelcules
Total (without water)207,09710
Polymers207,0569
Non-polymers401
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: microscopy
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area18620 Å2
ΔGint-194 kcal/mol
Surface area69930 Å2

-
Components

#1: Protein Protein EMRE homolog, mitochondrial-like Protein / EMRE


Mass: 7372.190 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Tribolium castaneum (red flour beetle) / Gene: TcasGA2_TC012057 / Production host: Homo sapiens (human) / References: UniProt: D6X268
#2: Protein
Calcium uniporter protein / MCU


Mass: 23634.100 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Tribolium castaneum (red flour beetle) / Gene: TcasGA2_TC013837 / Production host: Homo sapiens (human) / References: UniProt: D6WIX5
#3: Protein Calcium uptake protein 1, mitochondrial / Atopy-related autoantigen CALC / ara CALC / Calcium-binding atopy-related autoantigen 1 / MICU1


Mass: 45422.883 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MICU1, CALC, CBARA1 / Production host: Homo sapiens (human) / References: UniProt: Q9BPX6
#4: Protein Calcium uptake protein 2, mitochondrial / EF-hand domain-containing family member A1 / MICU2


Mass: 44980.609 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MICU2, EFHA1 / Production host: Homo sapiens (human) / References: UniProt: Q8IYU8
#5: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca
Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Mitochondrial Calcium Uniporter holocomplexCOMPLEX#1-#40MULTIPLE SOURCES
2EMRECOMPLEX#11RECOMBINANT
3MCUCOMPLEX#21RECOMBINANT
4MICU1-MICU2 heterodimerCOMPLEX#3-#41RECOMBINANT
Molecular weightUnits: MEGADALTONS / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Tribolium castaneum (red flour beetle)7070
23Tribolium castaneum (red flour beetle)7070
34Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
12Homo sapiens (human)9606Expi293, Invitrogen
23Homo sapiens (human)9606Expi293, Invitrogen
34Homo sapiens (human)9606Expi293, Invitrogen
Buffer solutionpH: 7.5
Buffer component
IDConc.NameFormulaBuffer-ID
120 mMHEPES1
2150 mMsodium chlorideNaClSodium chloride1
35 mMEGTA1
SpecimenConc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: Monodisperse sample
Specimen supportGrid material: GOLD / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 298 K / Details: 2 second blot, blot force of 0

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 22500 X / Nominal defocus max: -3000 nm / Nominal defocus min: -1000 nm / Alignment procedure: BASIC
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 4 sec. / Electron dose: 71 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 5 / Num. of real images: 21115
Image scansMovie frames/image: 40 / Used frames/image: 1-40

-
Processing

EM software
IDNameVersionCategory
2SerialEMimage acquisition
4CTFFIND4.1.5CTF correction
7Coot0.8.8model fitting
9cryoSPARCv2.12.4initial Euler assignment
10RELION3initial Euler assignment
11RELION3final Euler assignment
12cryoSPARCv2.12.4classification
13RELION33D reconstruction
14PHENIX1.17.1-3660model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 17440131
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 350160 / Algorithm: FOURIER SPACE / Symmetry type: POINT
Atomic model buildingB value: 124 / Protocol: AB INITIO MODEL / Space: REAL / Target criteria: Correlation coefficient

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242):Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more