Protein or peptide: ER membrane protein complex subunit 1Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 2Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 3Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 4Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 5Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 6Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 7Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 8Endoplasmic reticulum
Protein or peptide: ER membrane protein complex subunit 10Endoplasmic reticulum
Keywords
ER membrane protein complex / MEMBRANE PROTEIN
Function / homology
Function and homology information
inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / EMC complex / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / cobalt ion transmembrane transporter activity / Miscellaneous transport and binding events / tail-anchored membrane protein insertion into ER membrane / magnesium ion transmembrane transporter activity ...inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / EMC complex / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / magnesium ion transport / cobalt ion transmembrane transporter activity / Miscellaneous transport and binding events / tail-anchored membrane protein insertion into ER membrane / magnesium ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / protein folding in endoplasmic reticulum / copper ion transport / autophagosome assembly / RHOA GTPase cycle / positive regulation of endothelial cell proliferation / positive regulation of endothelial cell migration / positive regulation of angiogenesis / early endosome membrane / carbohydrate binding / angiogenesis / early endosome / Golgi membrane / apoptotic process / endoplasmic reticulum membrane / Golgi apparatus / endoplasmic reticulum / protein-containing complex / extracellular region / membrane / plasma membrane / cytoplasm Similarity search - Function
ER membrane protein complex subunit 8/9 / Uncharacterised protein family (UPF0172) / TMEM85/ER membrane protein complex subunit 4 / Protein of unknown function (DUF1077) / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 7 / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 6 / ER membrane protein complex subunit 3 / ER membrane protein complex subunit 1, C-terminal ...ER membrane protein complex subunit 8/9 / Uncharacterised protein family (UPF0172) / TMEM85/ER membrane protein complex subunit 4 / Protein of unknown function (DUF1077) / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 7 / ER membrane protein complex subunit 7, beta-sandwich domain / ER membrane protein complex subunit 6 / ER membrane protein complex subunit 3 / ER membrane protein complex subunit 1, C-terminal / Membrane magnesium transporter / ER membrane protein complex subunit 1 / ER membrane protein complex subunit 6-like / EMC6 / ER membrane protein complex subunit 1, C-terminal / Membrane magnesium transporter / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 2-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein DUF106 / Carbohydrate-binding-like fold / Pyrrolo-quinoline quinone repeat / PQQ-like domain / Tetratricopeptide repeat / Quinoprotein alcohol dehydrogenase-like superfamily / TPR repeat region circular profile. / TPR repeat profile. / MPN domain / MPN domain profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Tetratricopeptide-like helical domain superfamily / WD40/YVTN repeat-like-containing domain superfamily Similarity search - Domain/homology
ER membrane protein complex subunit 8 / ER membrane protein complex subunit 2 / ER membrane protein complex subunit 4 / ER membrane protein complex subunit 10 / ER membrane protein complex subunit 5 / ER membrane protein complex subunit 1 / ER membrane protein complex subunit 6 / Endoplasmic reticulum membrane protein complex subunit 7 / ER membrane protein complex subunit 3 Similarity search - Component
Biological species
Homo sapiens (human)
Method
single particle reconstruction / cryo EM / Resolution: 3.47 Å
National Natural Science Foundation of China (NSFC)
31930063
China
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.
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