登録情報 データベース : EMDB / ID : EMD-48085 ダウンロードとリンクタイトル Import stalled PINK1 TOM complex, extended TOM20 helix class マップデータMain map 詳細 試料複合体 : Complex of VDAC, TOM core and PINK1タンパク質・ペプチド : Serine/threonine-protein kinase PINK1, mitochondrialタンパク質・ペプチド : Mitochondrial import receptor subunit TOM20 homologタンパク質・ペプチド : Non-selective voltage-gated ion channel VDAC2タンパク質・ペプチド : Mitochondrial import receptor subunit TOM40 homologタンパク質・ペプチド : Mitochondrial import receptor subunit TOM5 homologタンパク質・ペプチド : Mitochondrial import receptor subunit TOM7 homologタンパク質・ペプチド : Mitochondrial import receptor subunit TOM6 homologタンパク質・ペプチド : Mitochondrial import receptor subunit TOM22 homolog 残り4件を表示 表示を減らすリガンド : 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE 詳細 キーワード PINK1 / TOM complex / VDAC / TRANSLOCASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
positive regulation of free ubiquitin chain polymerization / positive regulation of synaptic transmission, dopaminergic / positive regulation of cristae formation / tRNA import into mitochondrion / TOM complex / mitochondrial outer membrane permeabilization / mitochondrial transmembrane transport / voltage-gated monoatomic anion channel activity / : / Mitochondrial calcium ion transport ... positive regulation of free ubiquitin chain polymerization / positive regulation of synaptic transmission, dopaminergic / positive regulation of cristae formation / tRNA import into mitochondrion / TOM complex / mitochondrial outer membrane permeabilization / mitochondrial transmembrane transport / voltage-gated monoatomic anion channel activity / : / Mitochondrial calcium ion transport / mitochondrion to lysosome vesicle-mediated transport / maintenance of protein location in mitochondrion / mitochondrion targeting sequence binding / : / mitochondrial outer membrane translocase complex / cellular response to hydrogen sulfide / protein kinase B binding / regulation of autophagy of mitochondrion / phospholipid scramblase activity / protein insertion into mitochondrial outer membrane / regulation of synaptic vesicle transport / ceramide binding / dopamine secretion / mitochondria-associated endoplasmic reticulum membrane contact site / positive regulation of mitochondrial electron transport, NADH to ubiquinone / regulation of oxidative phosphorylation / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / negative regulation of hydrogen peroxide-induced neuron intrinsic apoptotic signaling pathway / C3HC4-type RING finger domain binding / protein-transporting ATPase activity / migrasome / regulation of hydrogen peroxide metabolic process / regulation of cellular response to oxidative stress / negative regulation of autophagosome assembly / voltage-gated monoatomic ion channel activity / positive regulation of dopamine secretion / autophagy of mitochondrion / phosphatidylcholine binding / positive regulation of type 2 mitophagy / oxysterol binding / binding of sperm to zona pellucida / Mitochondrial protein import / TORC2 signaling / cellular response to toxic substance / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / regulation of mitochondrion organization / monoatomic anion transport / negative regulation of JNK cascade / : / : / phospholipid translocation / regulation of reactive oxygen species metabolic process / peptidase activator activity / positive regulation of mitochondrial fission / cholesterol binding / astrocyte projection / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / negative regulation of macroautophagy / porin activity / FOXO-mediated transcription of cell death genes / pore complex / negative regulation of mitophagy / Lewy body / protein import into mitochondrial matrix / negative regulation of intrinsic apoptotic signaling pathway / positive regulation of release of cytochrome c from mitochondria / hemopoiesis / negative regulation of reactive oxygen species metabolic process / positive regulation of ATP biosynthetic process / mitochondrial nucleoid / positive regulation of macroautophagy / regulation of protein ubiquitination / transmembrane protein transporter activity / regulation of protein-containing complex assembly / negative regulation of mitochondrial fission / mitophagy / regulation of proteasomal protein catabolic process / monoatomic ion transport / acrosomal vesicle / response to ischemia / positive regulation of protein ubiquitination / PINK1-PRKN Mediated Mitophagy / regulation of mitochondrial membrane potential / cell periphery / respiratory electron transport chain / positive regulation of translation / macroautophagy / mitochondrion organization / regulation of protein stability / intracellular protein transport / mitochondrial intermembrane space / mitochondrial membrane / kinase binding / kinase activity / : / protein transport / growth cone / cell body / cellular response to oxidative stress / protease binding 類似検索 - 分子機能 PINK1, protein kinase domain / Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / Protein import receptor MAS20, metazoan / Protein import receptor MAS20 / Mitochondrial outer membrane translocase complex, Tom20 domain superfamily / MAS20 protein import receptor ... PINK1, protein kinase domain / Mitochondrial import receptor subunit TOM5, metazoa / Mitochondrial import receptor subunit TOM6 homologue / Mitochondrial import receptor subunit TOM6 homolog / Eukaryotic mitochondrial porin signature. / Porin, eukaryotic type / Protein import receptor MAS20, metazoan / Protein import receptor MAS20 / Mitochondrial outer membrane translocase complex, Tom20 domain superfamily / MAS20 protein import receptor / : / Mitochondrial outer membrane translocase complex, subunit Tom5 / Mitochondrial import receptor subunit or translocase / Mitochondrial import receptor subunit Tom22 / Mitochondrial import receptor subunit TOM7 / Mitochondrial import receptor subunit Tom22 / TOM7 family / Tom40 / Eukaryotic porin/Tom40 / Eukaryotic porin / Porin domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Mitochondrial import receptor subunit TOM40 homolog / Non-selective voltage-gated ion channel VDAC2 / Mitochondrial import receptor subunit TOM20 homolog / Mitochondrial import receptor subunit TOM5 homolog / Mitochondrial import receptor subunit TOM6 homolog / Serine/threonine-protein kinase PINK1, mitochondrial / Mitochondrial import receptor subunit TOM22 homolog / Mitochondrial import receptor subunit TOM7 homolog 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.3 Å 詳細 データ登録者Kirk NS / Glukhova A / Callegari S / Komander D 資金援助 オーストラリア, 2件 詳細 詳細を隠すOrganization Grant number 国 National Health and Medical Research Council (NHMRC, Australia) GNT1178122 オーストラリア Other private オーストラリア
引用ジャーナル : Science / 年 : 2025タイトル : Structure of human PINK1 at a mitochondrial TOM-VDAC array.著者 : Sylvie Callegari / Nicholas S Kirk / Zhong Yan Gan / Toby Dite / Simon A Cobbold / Andrew Leis / Laura F Dagley / Alisa Glukhova / David Komander / 要旨 : Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We ... Mutations in the ubiquitin kinase PINK1 cause early-onset Parkinson's disease, but how PINK1 is stabilized at depolarized mitochondrial translocase complexes has remained poorly understood. We determined a 3.1-angstrom resolution cryo-electron microscopy structure of dimeric human PINK1 stabilized at an endogenous array of mitochondrial translocase of the outer membrane (TOM) and voltage-dependent anion channel (VDAC) complexes. Symmetric arrangement of two TOM core complexes around a central VDAC2 dimer is facilitated by TOM5 and TOM20, both of which also bind PINK1 kinase C-lobes. PINK1 enters mitochondria through the proximal TOM40 barrel of the TOM core complex, guided by TOM7 and TOM22. Our structure explains how human PINK1 is stabilized at the TOM complex and regulated by oxidation, uncovers a previously unknown TOM-VDAC assembly, and reveals how a physiological substrate traverses TOM40 during translocation. 履歴 登録 2024年11月26日 - ヘッダ(付随情報) 公開 2025年3月12日 - マップ公開 2025年3月12日 - 更新 2025年4月30日 - 現状 2025年4月30日 処理サイト : RCSB / 状態 : 公開
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