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- EMDB-31904: Human TOM complex without cross-linking -

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Basic information

Entry
Database: EMDB / ID: EMD-31904
TitleHuman TOM complex without cross-linking
Map data
Sample
  • Complex: Human TOM complex without cross-linking
    • Protein or peptide: Mitochondrial import receptor subunit TOM6 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM5 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM7 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM22 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM40 homolog
  • Ligand: UNDECANE
  • Ligand: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE
KeywordsTOM core complex / Cryo-EM / TRANSLOCASE
Function / homology
Function and homology information


TOM complex / mitochondrion targeting sequence binding / mitochondrial outer membrane translocase complex / mitochondria-associated endoplasmic reticulum membrane contact site / positive regulation of mitophagy in response to mitochondrial depolarization / protein import into mitochondrial matrix / Mitochondrial protein import / protein targeting to mitochondrion / positive regulation of protein targeting to mitochondrion / protein insertion into mitochondrial outer membrane ...TOM complex / mitochondrion targeting sequence binding / mitochondrial outer membrane translocase complex / mitochondria-associated endoplasmic reticulum membrane contact site / positive regulation of mitophagy in response to mitochondrial depolarization / protein import into mitochondrial matrix / Mitochondrial protein import / protein targeting to mitochondrion / positive regulation of protein targeting to mitochondrion / protein insertion into mitochondrial outer membrane / porin activity / pore complex / protein transmembrane transporter activity / monoatomic ion transport / PINK1-PRKN Mediated Mitophagy / regulation of protein stability / mitochondrial outer membrane / mitochondrial inner membrane / mitochondrion / membrane / cytosol
Similarity search - Function
Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Mitochondrial import receptor subunit Tom22 / Mitochondrial import receptor subunit TOM7 / Mitochondrial import receptor subunit Tom22 / TOM7 family / Mitochondrial outer membrane translocase complex, subunit Tom5 / Mitochondrial import receptor subunit or translocase / Tom40 ...Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Mitochondrial import receptor subunit Tom22 / Mitochondrial import receptor subunit TOM7 / Mitochondrial import receptor subunit Tom22 / TOM7 family / Mitochondrial outer membrane translocase complex, subunit Tom5 / Mitochondrial import receptor subunit or translocase / Tom40 / Eukaryotic porin/Tom40 / Eukaryotic porin / Porin domain superfamily
Similarity search - Domain/homology
Mitochondrial import receptor subunit TOM40 homolog / Mitochondrial import receptor subunit TOM5 homolog / Mitochondrial import receptor subunit TOM6 homolog / Mitochondrial import receptor subunit TOM22 homolog / Mitochondrial import receptor subunit TOM7 homolog
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.53 Å
AuthorsLiu DS / Sui SF
Funding support China, 1 items
OrganizationGrant numberCountry
National Basic Research Program of China (973 Program) China
CitationJournal: Proc Natl Acad Sci U S A / Year: 2022
Title: Structural basis of Tom20 and Tom22 cytosolic domains as the human TOM complex receptors.
Authors: Jiayue Su / Desheng Liu / Fan Yang / Mei-Qing Zuo / Chang Li / Meng-Qiu Dong / Shan Sun / Sen-Fang Sui /
Abstract: Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex ...Mitochondrial preproteins synthesized in cytosol are imported into mitochondria by a multisubunit translocase of the outer membrane (TOM) complex. Functioned as the receptor, the TOM complex components, Tom 20, Tom22, and Tom70, recognize the presequence and further guide the protein translocation. Their deficiency has been linked with neurodegenerative diseases and cardiac pathology. Although several structures of the TOM complex have been reported by cryoelectron microscopy (cryo-EM), how Tom22 and Tom20 function as TOM receptors remains elusive. Here we determined the structure of TOM core complex at 2.53 Å and captured the structure of the TOM complex containing Tom22 and Tom20 cytosolic domains at 3.74 Å. Structural analysis indicates that Tom20 and Tom22 share a similar three-helix bundle structural feature in the cytosolic domain. Further structure-guided biochemical analysis reveals that the Tom22 cytosolic domain is responsible for binding to the presequence, and the helix H1 is critical for this binding. Altogether, our results provide insights into the functional mechanism of the TOM complex recognizing and transferring preproteins across the mitochondrial membrane.
History
DepositionSep 6, 2021-
Header (metadata) releaseJul 13, 2022-
Map releaseJul 13, 2022-
UpdateJun 19, 2024-
Current statusJun 19, 2024Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_31904.png

Downloads & links

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Map

FileDownload / File: emd_31904.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.8433 Å
Density
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-0.3727763 - 1.1065001
Average (Standard dev.)0.000063027976 (±0.033451386)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 269.856 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : Human TOM complex without cross-linking

EntireName: Human TOM complex without cross-linking
Components
  • Complex: Human TOM complex without cross-linking
    • Protein or peptide: Mitochondrial import receptor subunit TOM6 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM5 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM7 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM22 homolog
    • Protein or peptide: Mitochondrial import receptor subunit TOM40 homolog
  • Ligand: UNDECANE
  • Ligand: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE

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Supramolecule #1: Human TOM complex without cross-linking

SupramoleculeName: Human TOM complex without cross-linking / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Mitochondrial import receptor subunit TOM6 homolog

MacromoleculeName: Mitochondrial import receptor subunit TOM6 homolog / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 8.007988 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MASSTVPVSA AGSANETPEI PDNVGDWLRG VYRFATDRND FRRNLILNLG LFAAGVWLAR NLSDIDLMAP QPGV

UniProtKB: Mitochondrial import receptor subunit TOM6 homolog

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Macromolecule #2: Mitochondrial import receptor subunit TOM5 homolog

MacromoleculeName: Mitochondrial import receptor subunit TOM5 homolog / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 6.045318 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MFRIEGLAPK LDPEEMKRKM REDVISSIRN FLIYVALLRV TPFILKKLDS I

UniProtKB: Mitochondrial import receptor subunit TOM5 homolog

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Macromolecule #3: Mitochondrial import receptor subunit TOM7 homolog

MacromoleculeName: Mitochondrial import receptor subunit TOM7 homolog / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 6.256473 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MVKLSKEAKQ RLQQLFKGSQ FAIRWGFIPL VIYLGFKRGA DPGMPEPTVL SLLWG

UniProtKB: Mitochondrial import receptor subunit TOM7 homolog

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Macromolecule #4: Mitochondrial import receptor subunit TOM22 homolog

MacromoleculeName: Mitochondrial import receptor subunit TOM22 homolog / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 15.532528 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString:
MAAAVAAAGA GEPQSPDELL PKGDAEKPEE ELEEDDDEEL DETLSERLWG LTEMFPERVR SAAGATFDLS LFVAQKMYRF SRAALWIGT TSFMILVLPV VFETEKLQME QQQQLQQRQI LLGPNTGLSG GMPGALPSLP GKI

UniProtKB: Mitochondrial import receptor subunit TOM22 homolog

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Macromolecule #5: Mitochondrial import receptor subunit TOM40 homolog

MacromoleculeName: Mitochondrial import receptor subunit TOM40 homolog / type: protein_or_peptide / ID: 5 / Number of copies: 2 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.926926 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MGNVLAASSP PAGPPPPPAP ALVGLPPPPP SPPGFTLPPL GGSLGAGTST SRSSERTPGA ATASASGAAE DGACGCLPNP GTFEECHRK CKELFPIQME GVKLTVNKGL SNHFQVNHTV ALSTIGESNY HFGVTYVGTK QLSPTEAFPV LVGDMDNSGS L NAQVIHQL ...String:
MGNVLAASSP PAGPPPPPAP ALVGLPPPPP SPPGFTLPPL GGSLGAGTST SRSSERTPGA ATASASGAAE DGACGCLPNP GTFEECHRK CKELFPIQME GVKLTVNKGL SNHFQVNHTV ALSTIGESNY HFGVTYVGTK QLSPTEAFPV LVGDMDNSGS L NAQVIHQL GPGLRSKMAI QTQQSKFVNW QVDGEYRGSD FTAAVTLGNP DVLVGSGILV AHYLQSITPC LALGGELVYH RR PGEEGTV MSLAGKYTLN NWLATVTLGQ AGMHATYYHK ASDQLQVGVE FEASTRMQDT SVSFGYQLDL PKANLLFKGS VDS NWIVGA TLEKKLPPLP LTLALGAFLN HRKNKFQCGF GLTIG

UniProtKB: Mitochondrial import receptor subunit TOM40 homolog

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Macromolecule #6: UNDECANE

MacromoleculeName: UNDECANE / type: ligand / ID: 6 / Number of copies: 16 / Formula: UND
Molecular weightTheoretical: 156.308 Da
Chemical component information

ChemComp-UND:
UNDECANE

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Macromolecule #7: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE

MacromoleculeName: 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 7 / Number of copies: 27 / Formula: PC1
Molecular weightTheoretical: 790.145 Da
Chemical component information

ChemComp-PC1:
1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.4
Sugar embeddingMaterial: Digitonin
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 1.3 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.53 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 347651
Initial angle assignmentType: COMMON LINE
Final angle assignmentType: COMMON LINE

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