- EMDB-35907: cryo-EM structure of human EMC and VDAC -
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基本情報
登録情報
データベース: EMDB / ID: EMD-35907
タイトル
cryo-EM structure of human EMC and VDAC
マップデータ
試料
複合体: EMC_VDAC
タンパク質・ペプチド: ER membrane protein complex subunit 1
タンパク質・ペプチド: ER membrane protein complex subunit 2
タンパク質・ペプチド: ER membrane protein complex subunit 3
タンパク質・ペプチド: ER membrane protein complex subunit 4
タンパク質・ペプチド: ER membrane protein complex subunit 5
タンパク質・ペプチド: ER membrane protein complex subunit 6
タンパク質・ペプチド: ER membrane protein complex subunit 7
タンパク質・ペプチド: ER membrane protein complex subunit 8
タンパク質・ペプチド: ER membrane protein complex subunit 10
タンパク質・ペプチド: Voltage-dependent anion-selective channel protein 1
キーワード
ER membrane protein complex / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
negative regulation of calcium import into the mitochondrion / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / mitochondrial transmembrane transport / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / neuron-neuron synaptic transmission / magnesium ion transport ...negative regulation of calcium import into the mitochondrion / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / mitochondrial transmembrane transport / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / neuron-neuron synaptic transmission / magnesium ion transport / Mitochondrial calcium ion transport / tail-anchored membrane protein insertion into ER membrane / Miscellaneous transport and binding events / cobalt ion transmembrane transporter activity / regulation of autophagy of mitochondrion / calcium import into the mitochondrion / ferrous iron transmembrane transporter activity / ceramide binding / mitochondrial permeability transition pore complex / copper ion transport / magnesium ion transmembrane transporter activity / voltage-gated monoatomic ion channel activity / phosphatidylcholine binding / positive regulation of type 2 mitophagy / Mitochondrial protein import / oxysterol binding / Pyruvate metabolism / monoatomic anion transport / pyruvate metabolic process / cholesterol binding / lipid transport / porin activity / pore complex / mitochondrial nucleoid / negative regulation of reactive oxygen species metabolic process / autophagosome assembly / RHOA GTPase cycle / behavioral fear response / positive regulation of endothelial cell proliferation / epithelial cell differentiation / positive regulation of endothelial cell migration / learning / PINK1-PRKN Mediated Mitophagy / mitochondrial membrane / positive regulation of angiogenesis / carbohydrate binding / early endosome membrane / angiogenesis / mitochondrial outer membrane / transmembrane transporter binding / early endosome / Ub-specific processing proteases / positive regulation of apoptotic process / membrane raft / Golgi membrane / apoptotic process / synapse / endoplasmic reticulum membrane / negative regulation of apoptotic process / protein kinase binding / endoplasmic reticulum / Golgi apparatus / protein-containing complex / mitochondrion / extracellular exosome / extracellular region / ATP binding / identical protein binding / nucleus / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能
ER membrane protein complex subunit 8/9 / : / Uncharacterised protein family (UPF0172) / EMC2 TPR-like repeat domain / TMEM85/ER membrane protein complex subunit 4 / ER membrane protein complex subunit 4 / 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 8/9 / : / Uncharacterised protein family (UPF0172) / EMC2 TPR-like repeat domain / TMEM85/ER membrane protein complex subunit 4 / ER membrane protein complex subunit 4 / 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 / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / ER membrane protein complex subunit 2-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein EMC3/TMCO1-like / Integral membrane protein DUF106 / Eukaryotic porin/Tom40 / Eukaryotic porin / Carbohydrate-binding-like fold / Outer membrane protein assembly factor BamB / Pyrrolo-quinoline quinone repeat / Porin domain superfamily / 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 類似検索 - ドメイン・相同性
ER membrane protein complex subunit 8 / Non-selective voltage-gated ion channel VDAC1 / 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 類似検索 - 構成要素
National Natural Science Foundation of China (NSFC)
31930063
中国
引用
ジャーナル: Aging (Albany NY) / 年: 2024 タイトル: Structural insights into human EMC and its interaction with VDAC. 著者: Mingyue Li / Chunli Zhang / Yuntao Xu / Shaobai Li / Chenhui Huang / Jian Wu / Ming Lei / 要旨: 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.