[English] 日本語
Yorodumi
- EMDB-76655: Single particle cryo-EM structure of human MTCH2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-76655
TitleSingle particle cryo-EM structure of human MTCH2
Map data
Sample
  • Complex: MTCH2 complexed with UCP1 nanobody
    • Protein or peptide: Mitochondrial carrier homolog 2,Mitochondrial brown fat uncoupling protein 1
    • Protein or peptide: UCP1 Nanobody
Keywordsmitochondrial outer membrane insertase / SLC25 carrier fold / hydrophilic groove / membrane protein biogenesis / MEMBRANE PROTEIN
Function / homology
Function and homology information


regulation of mitochondrial fusion / purine ribonucleotide binding / cellular response to dehydroepiandrosterone / Mitochondrial Uncoupling / The fatty acid cycling model / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / membrane insertase activity / adaptive thermogenesis / protein insertion into mitochondrial outer membrane ...regulation of mitochondrial fusion / purine ribonucleotide binding / cellular response to dehydroepiandrosterone / Mitochondrial Uncoupling / The fatty acid cycling model / oxidative phosphorylation uncoupler activity / mitochondrial transmembrane transport / membrane insertase activity / adaptive thermogenesis / protein insertion into mitochondrial outer membrane / positive regulation of stem cell differentiation / diet induced thermogenesis / protein localization to mitochondrion / cardiolipin binding / cellular response to fatty acid / long-chain fatty acid binding / regulation of reactive oxygen species biosynthetic process / cellular response to cold / response to temperature stimulus / lipid homeostasis / proton transmembrane transporter activity / brown fat cell differentiation / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / cellular response to hormone stimulus / response to cold / transmembrane transporter activity / proton transmembrane transport / cellular response to reactive oxygen species / response to nutrient levels / GDP binding / positive regulation of cold-induced thermogenesis / mitochondrial outer membrane / mitochondrial inner membrane / positive regulation of apoptotic process / GTP binding / mitochondrion / membrane / nucleus
Similarity search - Function
: / Mitochondrial carrier protein / Mitochondrial substrate/solute carrier / Mitochondrial carrier domain superfamily / Mitochondrial carrier protein / Solute carrier (Solcar) repeat profile.
Similarity search - Domain/homology
Mitochondrial brown fat uncoupling protein 1 / Mitochondrial carrier homolog 2
Similarity search - Component
Biological speciesHomo sapiens (human) / synthetic construct (others)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsLuo Z / Stevens TA / Voorhees RM
Funding support United States, 8 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)1K99GM151478 United States
Nagendranath Reddy Graduate Fellowship United States
Hevolution/AFAR new investigator award United States
Caltech Center for Evolutionary Science Grant United States
Caltech OTCCP Rothenberg Innovation Initiative Grant United States
Merkin Institute Translational Research Grant United States
Sontag Foundation United States
Howard Hughes Medical Institute (HHMI)Freeman Hrabowski Scholar United States
CitationJournal: Sci Adv / Year: 2026
Title: Structural evolution of the MTCH family of mitochondrial insertases.
Authors: Taylor A Stevens / Zhilin Luo / Camryn Lee / Masami Hazu / Erini G Galatis / Alison J Inglis / Alina Guna / Rebecca M Voorhees /
Abstract: We demonstrate that MTCH2 is the defining member of a large family of mitochondrial outer membrane (OM) insertases. MTCH insertases are conserved across holozoa and have diverged from the solute ...We demonstrate that MTCH2 is the defining member of a large family of mitochondrial outer membrane (OM) insertases. MTCH insertases are conserved across holozoa and have diverged from the solute carrier 25 transporters. The cryoelectron microscopy structure of the 33-kilodalton human MTCH2 revealed that evolution of its insertase activity required loss of a transmembrane helix, which created a lipid-accessible hydrophilic groove stabilized by its unique, structured C terminus. Mutational analyses showed that MTCH insertase activity is attenuated, while experimental structures and reconstitution of hyperactive mutants demonstrated that the hydrophobicity, charge, and size of the residues that line its groove regulated MTCH function. Leveraging the MTCH2 structure, we identified the plant OM insertase and proposed a universal mechanism for OM insertion across all kingdoms of life.
History
DepositionApr 14, 2026-
Header (metadata) releaseMay 13, 2026-
Map releaseMay 13, 2026-
UpdateJul 8, 2026-
Current statusJul 8, 2026Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_76655.png

Downloads & links

-
Map

FileDownload / File: emd_76655.map.gz / Format: CCP4 / Size: 600.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 540 pix.
= 449.28 Å		0.83 Å/pix.
x 540 pix.
= 449.28 Å		0.83 Å/pix.
x 540 pix.
= 449.28 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.832 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.056
Minimum - Maximum-0.08943109 - 0.23142233
Average (Standard dev.)0.0000143861 (±0.0025389432)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions540540540
Spacing540540540
CellA=B=C: 449.28 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_76655_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_76655_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_76655_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : MTCH2 complexed with UCP1 nanobody

EntireName: MTCH2 complexed with UCP1 nanobody
Components
  • Complex: MTCH2 complexed with UCP1 nanobody
    • Protein or peptide: Mitochondrial carrier homolog 2,Mitochondrial brown fat uncoupling protein 1
    • Protein or peptide: UCP1 Nanobody

-
Supramolecule #1: MTCH2 complexed with UCP1 nanobody

SupramoleculeName: MTCH2 complexed with UCP1 nanobody / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Details: Human MTCH2 with the cytosolic loop between TM4 and TM5 replaced by the anti-UCP1 nanobody recognition epitope from UCP1 in complex with the anti-UCP1 nanobody pMb65 (modified to permit NabFab binding)
Source (natural)Organism: Homo sapiens (human) / Organelle: Mitochondrion / Location in cell: Mitochondrial outer membrane
Molecular weightTheoretical: 35 KDa

-
Macromolecule #1: Mitochondrial carrier homolog 2,Mitochondrial brown fat uncouplin...

MacromoleculeName: Mitochondrial carrier homolog 2,Mitochondrial brown fat uncoupling protein 1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 33.557191 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MADAASQVLL GSGLTILSQP LMYVKVLIQV GYEPLPPTIG RNIFGRQVCQ LPGLFSYAQH IASIDGRRGL FTGLTPRLCS GVLGTVVHG KVLQHYQESD KGEELGPGNV QKEVSSSFDH VIKETTREMI ARSAATLITH PFHVITLRSM VQFIGRESKY C GLCDSIIT ...String:
MADAASQVLL GSGLTILSQP LMYVKVLIQV GYEPLPPTIG RNIFGRQVCQ LPGLFSYAQH IASIDGRRGL FTGLTPRLCS GVLGTVVHG KVLQHYQESD KGEELGPGNV QKEVSSSFDH VIKETTREMI ARSAATLITH PFHVITLRSM VQFIGRESKY C GLCDSIIT IYREEGILGF FAGLVPRLLG DILSLWLCNS VYYLMKEAFV KNNILADDVP CHLVSQAVAG FFASMLTYPF VL VSNLMAV NNCGLAGGCP PYSPIYTSWI DCWCMLQKEG NMSRGNSLFF RKVPFGKTYC CDLKMLI

UniProtKB: Mitochondrial carrier homolog 2, Mitochondrial brown fat uncoupling protein 1, Mitochondrial carrier homolog 2

-
Macromolecule #2: UCP1 Nanobody

MacromoleculeName: UCP1 Nanobody / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: synthetic construct (others)
Molecular weightTheoretical: 13.913538 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString:
GQRQLVESGG GLVQPGGSLR LSCAASGRTS STYTMGWFRQ APGKEREFVA AISWTGTPYY ADSVKGRFTI SRDNAKNTVY LQMNSLEPE DTAVYYCAAA RPGLFIFVSD YARTAKYDYW GKGTPVTV

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration5.9 mg/mL
BufferpH: 7.5
Component:
ConcentrationFormulaName
50.0 mMHEPES/KOH4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid/potassium hydroxide
2.0 mMMgOAcmagnesium acetate
0.07 %UDMn-Undecyl-beta-D-Maltopyranoside
200.0 mMNaClsodium chloride

Details: 50 mM HEPES/KOH pH 7.5, 200 mM NaCl, 2 mM Mg Acetate, and 0.07% UDM
GridModel: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Support film - Film thickness: 12 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.03 kPa
Details: The grid was glow-discharged with a PELCO easiGlowTM (Ted Pella, Inc.) at 20 mA for 60 s.
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279.15 K / Instrument: FEI VITROBOT MARK IV

-
Electron microscopy

MicroscopeTFS KRIOS
SoftwareName: SerialEM
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 11520 pixel / Digitization - Dimensions - Height: 8184 pixel / Number grids imaged: 1 / Number real images: 15334 / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 70.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.6 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 105000
Sample stageSpecimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 4791546
Details: 14,190 out of 15,334 micrographs were selected for downstream processing. A total of 4,791,546 particles from blob picker and template picker were obtained. After running 11 rounds of ...Details: 14,190 out of 15,334 micrographs were selected for downstream processing. A total of 4,791,546 particles from blob picker and template picker were obtained. After running 11 rounds of heterogenous refinement, 485,622 particles were selected for further processing.
CTF correctionSoftware - Name: cryoSPARC (ver. 4.7.0)
Details: CTF parameters estimated using Patch CTF estimation in cryoSPARC. Global CTF correction for beam tilt was additionally performed.
Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionNumber classes used: 5 / Applied symmetry - Point group: C1 (asymmetric) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.7.0)
Details: Final map generated by local refinement in cryoSPARC using a soft mask encompassing MTCH2 only.
Number images used: 485622
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.7.0) / Details: Ab initio reconstruction in cryoSPARC
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 4.7.0)
Details: Local refinement in cryoSPARC with a soft mask around MTCH2 only
Final 3D classificationNumber classes: 5 / Software - Name: cryoSPARC (ver. 4.7.0) / Details: Heterogeneous refinement in cryoSPARC
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial model
ChainPDB ID
chain_id: A, source_name: AlphaFold, initial_model_type: in silico model
chain_id: B, source_name: PDB, initial_model_type: experimental model

8hbv

SoftwareName: Coot (ver. 0.9.8.95)
DetailsInitial fitting was done using Coot and refined by Phenix cryo-EM real space refinement.
RefinementSpace: REAL / Protocol: FLEXIBLE FIT / Overall B value: 136 / Target criteria: Real-space correlation coefficient
Output model

PDB-12oy:
Single particle cryo-EM structure of human MTCH2

+
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