+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8auk | ||||||
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タイトル | Cryo-EM structure of human BIRC6 in complex with HTRA2. | ||||||
要素 |
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キーワード | LIGASE / E3 ubiquitin ligase / E2/E3 hybrid / inhibitor of apoptosis protein | ||||||
機能・相同性 | 機能・相同性情報 HtrA2 peptidase / pentacyclic triterpenoid metabolic process / negative regulation of mitophagy in response to mitochondrial depolarization / spongiotrophoblast layer development / ceramide metabolic process / regulation of autophagy of mitochondrion / mitochondrial protein catabolic process / CD40 receptor complex / labyrinthine layer development / programmed cell death ...HtrA2 peptidase / pentacyclic triterpenoid metabolic process / negative regulation of mitophagy in response to mitochondrial depolarization / spongiotrophoblast layer development / ceramide metabolic process / regulation of autophagy of mitochondrion / mitochondrial protein catabolic process / CD40 receptor complex / labyrinthine layer development / programmed cell death / ALK mutants bind TKIs / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / protein serine/threonine kinase inhibitor activity / Flemming body / serine-type endopeptidase complex / adult walking behavior / response to herbicide / microtubule organizing center / positive regulation of protein targeting to mitochondrion / execution phase of apoptosis / cysteine-type endopeptidase inhibitor activity / positive regulation of execution phase of apoptosis / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / ubiquitin conjugating enzyme activity / ubiquitin ligase inhibitor activity / protein autoprocessing / negative regulation of cell cycle / regulation of multicellular organism growth / cellular response to interferon-beta / neuron development / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / cellular response to retinoic acid / forebrain development / Mitochondrial protein degradation / serine-type peptidase activity / regulation of cytokinesis / mitochondrion organization / negative regulation of extrinsic apoptotic signaling pathway / mitochondrial membrane / trans-Golgi network / RING-type E3 ubiquitin transferase / protein catabolic process / mitochondrial intermembrane space / cytoplasmic side of plasma membrane / cellular response to growth factor stimulus / spindle pole / ubiquitin-protein transferase activity / intrinsic apoptotic signaling pathway in response to DNA damage / unfolded protein binding / Signaling by ALK fusions and activated point mutants / peptidase activity / regulation of cell population proliferation / cellular response to oxidative stress / cellular response to heat / midbody / neuron apoptotic process / negative regulation of neuron apoptotic process / cell population proliferation / cytoskeleton / intracellular signal transduction / endosome / protein ubiquitination / positive regulation of apoptotic process / cell division / protein phosphorylation / serine-type endopeptidase activity / centrosome / positive regulation of cell population proliferation / endoplasmic reticulum membrane / chromatin / negative regulation of apoptotic process / apoptotic process / endoplasmic reticulum / mitochondrion / proteolysis / identical protein binding / membrane / nucleus / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6.2 Å | ||||||
データ登録者 | Ehrmann, J.F. / Grabarczyk, D.B. / Clausen, T. | ||||||
資金援助 | European Union, 1件
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引用 | ジャーナル: Science / 年: 2023 タイトル: Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex. 著者: Julian F Ehrmann / Daniel B Grabarczyk / Maria Heinke / Luiza Deszcz / Robert Kurzbauer / Otto Hudecz / Alexandra Shulkina / Rebeca Gogova / Anton Meinhart / Gijs A Versteeg / Tim Clausen / 要旨: Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally ...Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8auk.cif.gz | 1.3 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8auk.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 8auk.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/au/8auk ftp://data.pdbj.org/pub/pdb/validation_reports/au/8auk | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 532009.000 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: BIRC6, KIAA1289 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q9NR09, RING-type E3 ubiquitin transferase #2: タンパク質 | 分子量: 35001.820 Da / 分子数: 3 / Mutation: S306A / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: HTRA2, OMI, PRSS25 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: O43464, HtrA2 peptidase #3: 化合物 | 研究の焦点であるリガンドがあるか | N | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Human BIRC6 homodimer in complex with HTRA2 homotrimer タイプ: COMPLEX / Entity ID: #1-#2 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 1.17 MDa / 実験値: YES |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Trichoplusia ni, Escherichia coli |
緩衝液 | pH: 7.5 |
試料 | 濃度: 0.2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
-解析
ソフトウェア |
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EMソフトウェア | 名称: RELION / バージョン: 4 / カテゴリ: 3次元再構成 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 6.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 15780 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||
原子モデル構築 |
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精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 412.95 Å2 | ||||||||||||||||||||||||
拘束条件 |
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