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基本情報
登録情報 | データベース: PDB / ID: 7zr5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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タイトル | CryoEM structure of HSP90-CDC37-BRAF(V600E)-PP5(closed) complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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![]() | PROTEIN BINDING / Complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | ![]() regulation of type II interferon-mediated signaling pathway / response to arachidonate / HSP90-CDC37 chaperone complex / negative regulation of proteasomal protein catabolic process / peptidyl-threonine dephosphorylation / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / peptidyl-serine dephosphorylation / CD4-positive, alpha-beta T cell differentiation / dynein axonemal particle ...regulation of type II interferon-mediated signaling pathway / response to arachidonate / HSP90-CDC37 chaperone complex / negative regulation of proteasomal protein catabolic process / peptidyl-threonine dephosphorylation / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / peptidyl-serine dephosphorylation / CD4-positive, alpha-beta T cell differentiation / dynein axonemal particle / histone methyltransferase binding / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / receptor ligand inhibitor activity / Signalling to p38 via RIT and RIN / myeloid progenitor cell differentiation / positive regulation of type 2 mitophagy / head morphogenesis / ARMS-mediated activation / ATP-dependent protein binding / endothelial cell apoptotic process / positive regulation of protein localization to cell surface / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / negative regulation of fibroblast migration / positive regulation of D-glucose transmembrane transport / establishment of protein localization to membrane / positive regulation of axonogenesis / protein kinase regulator activity / protein folding chaperone complex / regulation of cyclin-dependent protein serine/threonine kinase activity / regulation of T cell differentiation / mitogen-activated protein kinase kinase binding / response to morphine / Negative feedback regulation of MAPK pathway / post-transcriptional regulation of gene expression / histone H2AXS139 phosphatase activity / RNA polymerase II CTD heptapeptide repeat Y1 phosphatase activity / RNA polymerase II CTD heptapeptide repeat T4 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S2 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S5 phosphatase activity / RNA polymerase II CTD heptapeptide repeat S7 phosphatase activity / MAP kinase serine/threonine phosphatase activity / calmodulin-dependent protein phosphatase activity / myosin phosphatase activity / Frs2-mediated activation / protein serine/threonine phosphatase activity / protein-serine/threonine phosphatase / positive regulation of axon regeneration / Respiratory syncytial virus genome replication / telomerase holoenzyme complex assembly / stress fiber assembly / positive regulation of transforming growth factor beta receptor signaling pathway / Uptake and function of diphtheria toxin / 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 / regulation of type I interferon-mediated signaling pathway / TPR domain binding / face development / phosphatase activity / MAP kinase kinase activity / Assembly and release of respiratory syncytial virus (RSV) virions / synaptic vesicle exocytosis / dendritic growth cone / thyroid gland development / phosphoprotein phosphatase activity / The NLRP3 inflammasome / protein phosphatase activator activity / Sema3A PAK dependent Axon repulsion / somatic stem cell population maintenance / MAP kinase kinase kinase activity / regulation of protein ubiquitination / HSF1-dependent transactivation / response to unfolded protein / HSF1 activation / telomere maintenance via telomerase / postsynaptic modulation of chemical synaptic transmission / Attenuation phase / chaperone-mediated protein complex assembly / negative regulation of endothelial cell apoptotic process / protein targeting / axonal growth cone / RHOBTB2 GTPase cycle / Purinergic signaling in leishmaniasis infection / response to cAMP / protein dephosphorylation / supramolecular fiber organization / positive regulation of peptidyl-serine phosphorylation / positive regulation of stress fiber assembly / : / DNA polymerase binding / heat shock protein binding 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: 3.9 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
履歴 |
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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 | ![]() | 417.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 322.2 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 | ![]() | 1.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.4 MB | 表示 | |
XML形式データ | ![]() | 72.6 KB | 表示 | |
CIF形式データ | ![]() | 110.6 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 | ![]() 14883MC ![]() 7zr0C ![]() 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 / 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: タンパク質 | | 分子量: 56020.387 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() 参照: UniProt: P53041, protein-serine/threonine phosphatase #5: 化合物 | 研究の焦点であるリガンドがあるか | Y | Has protein modification | 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 |
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由来(天然) |
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由来(組換発現) |
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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: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 105063 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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