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基本情報
登録情報 | データベース: PDB / ID: 7zr0 | ||||||
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タイトル | CryoEM structure of HSP90-CDC37-BRAF(V600E) complex. | ||||||
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![]() | CHAPERONE / Complex / PROTEIN BINDING | ||||||
機能・相同性 | ![]() regulation of type II interferon-mediated signaling pathway / : / HSP90-CDC37 chaperone complex / positive regulation of cyclin-dependent protein kinase activity / positive regulation of mitophagy in response to mitochondrial depolarization / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / dynein axonemal particle / CD4-positive, alpha-beta T cell differentiation ...regulation of type II interferon-mediated signaling pathway / : / HSP90-CDC37 chaperone complex / positive regulation of cyclin-dependent protein kinase activity / positive regulation of mitophagy in response to mitochondrial depolarization / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / dynein axonemal particle / CD4-positive, alpha-beta T cell differentiation / histone methyltransferase binding / trehalose metabolism in response to stress / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / Signalling to p38 via RIT and RIN / head morphogenesis / myeloid progenitor cell differentiation / ARMS-mediated activation / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / endothelial cell apoptotic process / positive regulation of protein localization to cell surface / ATP-dependent protein binding / protein kinase regulator activity / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / protein folding chaperone complex / mitogen-activated protein kinase kinase binding / negative regulation of protein metabolic process / regulation of T cell differentiation / positive regulation of tau-protein kinase activity / Negative feedback regulation of MAPK pathway / post-transcriptional regulation of gene expression / telomerase holoenzyme complex assembly / positive regulation of axonogenesis / Respiratory syncytial virus genome replication / regulation of cyclin-dependent protein serine/threonine kinase activity / Uptake and function of diphtheria toxin / Frs2-mediated activation / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / TPR domain binding / stress fiber assembly / positive regulation of axon regeneration / positive regulation of transforming growth factor beta receptor signaling pathway / Assembly and release of respiratory syncytial virus (RSV) virions / face development / synaptic vesicle exocytosis / dendritic growth cone / somatic stem cell population maintenance / MAP kinase kinase activity / regulation of type I interferon-mediated signaling pathway / positive regulation of phosphoprotein phosphatase activity / thyroid gland development / Sema3A PAK dependent Axon repulsion / The NLRP3 inflammasome / regulation of protein ubiquitination / HSF1-dependent transactivation / response to unfolded protein / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / telomere maintenance via telomerase / chaperone-mediated protein complex assembly / MAP kinase kinase kinase activity / HSF1 activation / Attenuation phase / protein targeting / cellular response to interleukin-4 / RHOBTB2 GTPase cycle / Purinergic signaling in leishmaniasis infection / negative regulation of endothelial cell apoptotic process / axonal growth cone / DNA polymerase binding / supramolecular fiber organization / positive regulation of substrate adhesion-dependent cell spreading / Signaling by ERBB2 / : / positive regulation of stress fiber assembly / response to cAMP / heat shock protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / cellular response to calcium ion / ERK1 and ERK2 cascade / nitric-oxide synthase regulator activity / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling / substrate adhesion-dependent cell spreading / cellular response to nerve growth factor stimulus / thymus development / long-term synaptic potentiation / positive regulation of cell differentiation / ATP-dependent protein folding chaperone 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.4 Å | ||||||
![]() | Oberoi, J. / Pearl, L.H. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation. 著者: Jasmeen Oberoi / Xavi Aran Guiu / Emily A Outwin / Pascale Schellenberger / Theodoros I Roumeliotis / Jyoti S Choudhary / Laurence H Pearl / ![]() 要旨: Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client ...Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC37 system depends on the Ser/Thr phosphatase PP5, which associates with HSP90 via its N-terminal TPR domain. Here, we present the cryoEM structure of the oncogenic protein kinase client BRAF bound to HSP90-CDC37, showing how the V600E mutation favours BRAF association with HSP90-CDC37. Structures of HSP90-CDC37-BRAF complexes with PP5 in autoinhibited and activated conformations, together with proteomic analysis of its phosphatase activity on BRAF and CRAF, reveal how PP5 is activated by recruitment to HSP90 complexes. PP5 comprehensively dephosphorylates client proteins, removing interaction sites for regulatory partners such as 14-3-3 proteins and thus performing a 'factory reset' of the kinase prior to release. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 368.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 288.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 974.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1001.4 KB | 表示 | |
XML形式データ | ![]() | 63.8 KB | 表示 | |
CIF形式データ | ![]() | 94.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 14875MC ![]() 7zr5C ![]() 7zr6C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 86223.469 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #2: タンパク質 | | 分子量: 46853.816 Da / 分子数: 1 / Mutation: V600E / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() #3: タンパク質 | | 分子量: 90934.508 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: P15056, non-specific serine/threonine protein kinase #4: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
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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 |
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試料調製
構成要素 | 名称: HSP90-CDC37-BRAF(V600E) complex / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() |
緩衝液 | pH: 7.5 |
試料 | 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 |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1300 nm |
撮影 | 電子線照射量: 45 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 400624 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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