- 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小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 2小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 3小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 4小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 5小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 6小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 7小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 8小胞体
タンパク質・ペプチド: ER membrane protein complex subunit 10小胞体
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 (小胞体) / MEMBRANE PROTEIN (膜タンパク質)
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 / inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / 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 / inorganic cation transmembrane transporter activity / extrinsic component of endoplasmic reticulum membrane / 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 / Miscellaneous transport and binding events / ceramide binding / tail-anchored membrane protein insertion into ER membrane / magnesium ion transmembrane transporter activity / ferrous iron transmembrane transporter activity / regulation of autophagy of mitochondrion / mitochondrial permeability transition pore complex / protein folding in endoplasmic reticulum / ピルビン酸 / copper ion transport / Mitochondrial protein import / phosphatidylcholine binding / 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 / 学習 / ミトコンドリア / positive regulation of angiogenesis / early endosome membrane / carbohydrate binding / 血管新生 / mitochondrial outer membrane / transmembrane transporter binding / エンドソーム / Ub-specific processing proteases / 脂質ラフト / ゴルジ体 / apoptotic process / シナプス / endoplasmic reticulum membrane / negative regulation of apoptotic process / protein kinase binding / ゴルジ体 / 小胞体 / protein-containing complex / ミトコンドリア / extracellular exosome / extracellular region / 生体膜 / identical protein binding / 細胞核 / 細胞膜 / 細胞質 類似検索 - 分子機能
ER membrane protein complex subunit 8/9 / Uncharacterised protein family (UPF0172) / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / 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 8/9 / Uncharacterised protein family (UPF0172) / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / 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 / Voltage-dependent anion-selective channel protein 1 / 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.