登録情報 データベース : EMDB / ID : EMD-14875 ダウンロードとリンクタイトル CryoEM structure of HSP90-CDC37-BRAF(V600E) complex. マップデータ 詳細 試料複合体 : HSP90-CDC37-BRAF(V600E) complexタンパク質・ペプチド : Heat shock protein HSP 90-betaタンパク質・ペプチド : Hsp90 co-chaperone Cdc37タンパク質・ペプチド : Serine/threonine-protein kinase B-rafリガンド : ADENOSINE-5'-TRIPHOSPHATE 詳細機能・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
regulation of type II interferon-mediated signaling pathway / receptor ligand inhibitor activity / HSP90-CDC37 chaperone complex / 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 ... regulation of type II interferon-mediated signaling pathway / receptor ligand inhibitor activity / HSP90-CDC37 chaperone complex / 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 / 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 / negative regulation of fibroblast migration / positive regulation of glucose transmembrane transport / establishment of protein localization to membrane / protein kinase regulator activity / protein folding chaperone complex / MAP kinase kinase kinase activity / mitogen-activated protein kinase kinase binding / regulation of T cell differentiation / 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 / Uptake and function of diphtheria toxin / regulation of cyclin-dependent protein serine/threonine kinase activity / 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 / dendritic growth cone / synaptic vesicle exocytosis / somatic stem cell population maintenance / MAP kinase kinase activity / regulation of type I interferon-mediated signaling pathway / : / thyroid gland development / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / The NLRP3 inflammasome / Signaling by ERBB2 / telomere maintenance via telomerase / HSF1-dependent transactivation / response to unfolded protein / chaperone-mediated protein complex assembly / HSF1 activation / Attenuation phase / protein targeting / cellular response to interleukin-4 / RHOBTB2 GTPase cycle / negative regulation of endothelial cell apoptotic process / axonal growth cone / Purinergic signaling in leishmaniasis infection / DNA polymerase binding / supramolecular fiber organization / positive regulation of substrate adhesion-dependent cell spreading / chaperone-mediated protein folding / positive regulation of stress fiber assembly / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / protein folding chaperone / 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 / substrate adhesion-dependent cell spreading / ESR-mediated signaling / Signaling by ERBB2 TMD/JMD mutants / cellular response to nerve growth factor stimulus / thymus development / peptide binding / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / epidermal growth factor receptor signaling pathway 類似検索 - 分子機能 Cdc37, C-terminal / Cdc37, Hsp90 binding / Cdc37, Hsp90-binding domain superfamily / Cdc37 C terminal domain / Cdc37 Hsp90 binding domain / Cdc37 C terminal domain / Cdc37 Hsp90 binding domain / Cdc37 N terminal kinase binding / Cdc37 / Cdc37, N-terminal domain ... Cdc37, C-terminal / Cdc37, Hsp90 binding / Cdc37, Hsp90-binding domain superfamily / Cdc37 C terminal domain / Cdc37 Hsp90 binding domain / Cdc37 C terminal domain / Cdc37 Hsp90 binding domain / Cdc37 N terminal kinase binding / Cdc37 / Cdc37, N-terminal domain / Cdc37 N terminal kinase binding / Raf-like Ras-binding domain / Raf-like Ras-binding / Ras-binding domain (RBD) profile. / Raf-like Ras-binding domain / Diacylglycerol/phorbol-ester binding / : / Phorbol esters/diacylglycerol binding domain (C1 domain) / Zinc finger phorbol-ester/DAG-type signature. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / C1-like domain superfamily / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat shock protein Hsp90 family / Hsp90 protein / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase / Histidine kinase/HSP90-like ATPase superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / Ribosomal protein S5 domain 2-type fold / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Heat shock protein HSP 90-beta / Serine/threonine-protein kinase B-raf / Hsp90 co-chaperone Cdc37 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 : 3.4 Å 詳細 データ登録者Oberoi J / Pearl LH 資金援助 英国, 1件 詳細 詳細を隠すOrganization Grant number 国 Wellcome Trust 英国
引用ジャーナル : Nat Commun / 年 : 2022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 登録 2022年5月3日 - ヘッダ(付随情報) 公開 2022年12月14日 - マップ公開 2022年12月14日 - 更新 2023年1月11日 - 現状 2023年1月11日 処理サイト : PDBe / 状態 : 公開
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