- 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 / positive regulation of parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / neuron-neuron synaptic transmission / 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 / extrinsic component of endoplasmic reticulum membrane / inorganic cation transmembrane transporter activity / EMC complex / voltage-gated monoatomic anion channel activity / omegasome membrane / protein insertion into ER membrane by stop-transfer membrane-anchor sequence / neuron-neuron synaptic transmission / 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 / calcium import into the mitochondrion / ferrous iron transmembrane transporter activity / magnesium ion transmembrane transporter activity / regulation of autophagy of mitochondrion / mitochondrial permeability transition pore complex / copper ion transport / Mitochondrial protein import / phosphatidylcholine binding / Pyruvate metabolism / oxysterol binding / monoatomic anion transport / pyruvate metabolic process / cholesterol binding / porin activity / pore complex / mitochondrial nucleoid / autophagosome assembly / RHOA GTPase cycle / negative regulation of reactive oxygen species metabolic process / behavioral fear response / positive regulation of endothelial cell proliferation / epithelial cell differentiation / PINK1-PRKN Mediated Mitophagy / positive regulation of endothelial cell migration / learning / mitochondrial membrane / positive regulation of angiogenesis / early endosome membrane / carbohydrate binding / angiogenesis / transmembrane transporter binding / mitochondrial outer membrane / early endosome / Ub-specific processing proteases / membrane raft / Golgi membrane / synapse / endoplasmic reticulum membrane / negative regulation of apoptotic process / apoptotic process / protein kinase binding / Golgi apparatus / endoplasmic reticulum / protein-containing complex / mitochondrion / extracellular exosome / extracellular region / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm 類似検索 - 分子機能
: / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / 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 ...: / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / 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 / Eukaryotic porin/Tom40 / Eukaryotic porin / Carbohydrate-binding-like fold / Pyrrolo-quinoline quinone repeat / PQQ-like domain / Tetratricopeptide 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.