+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-35907 | |||||||||
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Title | cryo-EM structure of human EMC and VDAC | |||||||||
Map data | ||||||||||
Sample |
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Keywords | ER membrane protein complex / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information negative regulation of calcium import into the mitochondrion / positive regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization / inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / neuron-neuron synaptic transmission / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / Mitochondrial calcium ion transport ...negative regulation of calcium import into the mitochondrion / positive regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization / inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / neuron-neuron synaptic transmission / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / Mitochondrial calcium ion transport / magnesium ion transport / cobalt ion transmembrane transporter activity / tail-anchored membrane protein insertion into ER membrane / Miscellaneous transport and binding events / ceramide binding / magnesium ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / regulation of autophagy of mitochondrion / mitochondrial permeability transition pore complex / Pyruvate metabolism / copper ion transport / Mitochondrial protein import / phosphatidylcholine binding / pyruvate metabolic process / oxysterol binding / monoatomic anion transport / cholesterol binding / porin activity / mitochondrial nucleoid / pore complex / autophagosome assembly / RHOA GTPase cycle / negative regulation of reactive oxygen species metabolic process / behavioral fear response / epithelial cell differentiation / PINK1-PRKN Mediated Mitophagy / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / learning / mitochondrial membrane / positive regulation of angiogenesis / early endosome membrane / carbohydrate binding / angiogenesis / mitochondrial outer membrane / transmembrane transporter binding / early endosome / Ub-specific processing proteases / membrane raft / Golgi membrane / synapse / apoptotic process / endoplasmic reticulum membrane / negative regulation of apoptotic process / protein kinase binding / Golgi apparatus / endoplasmic reticulum / protein-containing complex / mitochondrion / extracellular exosome / extracellular region / membrane / identical protein binding / nucleus / plasma membrane / cytoplasm Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.32 Å | |||||||||
Authors | Li M / Zhang C / Wu J / Lei M | |||||||||
Funding support | China, 1 items
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Citation | Journal: Aging (Albany NY) / Year: 2024 Title: Structural insights into human EMC and its interaction with VDAC. Authors: Mingyue Li / Chunli Zhang / Yuntao Xu / Shaobai Li / Chenhui Huang / Jian Wu / Ming Lei / Abstract: The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in ...The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved, multi-subunit complex acting as an insertase at the ER membrane. Growing evidence shows that the EMC is also involved in stabilizing and trafficking membrane proteins. However, the structural basis and regulation of its multifunctionality remain elusive. Here, we report cryo-electron microscopy structures of human EMC in apo- and voltage-dependent anion channel (VDAC)-bound states at resolutions of 3.47 Å and 3.32 Å, respectively. We discovered a specific interaction between VDAC proteins and the EMC at mitochondria-ER contact sites, which is conserved from yeast to humans. Moreover, we identified a gating plug located inside the EMC hydrophilic vestibule, the substrate-binding pocket for client insertion. Conformation changes of this gating plug during the apo-to-VDAC-bound transition reveal that the EMC unlikely acts as an insertase in the VDAC1-bound state. Based on the data analysis, the gating plug may regulate EMC functions by modifying the hydrophilic vestibule in different states. Our discovery offers valuable insights into the structural basis of EMC's multifunctionality. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_35907.map.gz | 83.5 MB | EMDB map data format | |
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Header (meta data) | emd-35907-v30.xml emd-35907.xml | 24.9 KB 24.9 KB | Display Display | EMDB header |
Images | emd_35907.png | 57.4 KB | ||
Filedesc metadata | emd-35907.cif.gz | 7.4 KB | ||
Others | emd_35907_additional_1.map.gz emd_35907_half_map_1.map.gz emd_35907_half_map_2.map.gz | 157.1 MB 154.4 MB 154.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-35907 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-35907 | HTTPS FTP |
-Related structure data
Related structure data | 8j0oMC 8j0nC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_35907.map.gz / Format: CCP4 / Size: 166.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.09 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: #1
File | emd_35907_additional_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_35907_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_35907_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : EMC_VDAC
+Supramolecule #1: EMC_VDAC
+Macromolecule #1: ER membrane protein complex subunit 1
+Macromolecule #2: ER membrane protein complex subunit 2
+Macromolecule #3: ER membrane protein complex subunit 3
+Macromolecule #4: ER membrane protein complex subunit 4
+Macromolecule #5: ER membrane protein complex subunit 5
+Macromolecule #6: ER membrane protein complex subunit 6
+Macromolecule #7: ER membrane protein complex subunit 7
+Macromolecule #8: ER membrane protein complex subunit 8
+Macromolecule #9: ER membrane protein complex subunit 10
+Macromolecule #10: Voltage-dependent anion-selective channel protein 1
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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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 / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.2 µm |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: INSILICO MODEL |
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Initial angle assignment | Type: COMMON LINE |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 455504 |