登録情報 データベース : EMDB / ID : EMD-14473 ダウンロードとリンクタイトル Structure of the RAF1-HSP90-CDC37 complex (RHC-I) マップデータ 詳細 試料複合体 : RAF1-HSP90-CDC37 complex, RHC-Iタンパク質・ペプチド : Heat shock protein HSP 90-betaタンパク質・ペプチド : RAF proto-oncogene serine/threonine-protein kinaseタンパク質・ペプチド : Hsp90 co-chaperone Cdc37リガンド : ADENOSINE-5'-TRIPHOSPHATEリガンド : MAGNESIUM ION 詳細 キーワード RAF1-HSP90-CDC37 / complex / proto-oncogene / transferase / serine/threonine kinase / cancer / chaperone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 / HSP90-CDC37 chaperone complex / death-inducing signaling complex assembly / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / intermediate filament cytoskeleton organization / dynein axonemal particle / histone methyltransferase binding / receptor ligand inhibitor activity ... regulation of type II interferon-mediated signaling pathway / HSP90-CDC37 chaperone complex / death-inducing signaling complex assembly / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / intermediate filament cytoskeleton organization / dynein axonemal particle / histone methyltransferase binding / receptor ligand inhibitor activity / type B pancreatic cell proliferation / regulation of Rho protein signal transduction / positive regulation of type 2 mitophagy / ATP-dependent protein binding / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / positive regulation of protein localization to cell surface / Rap1 signalling / regulation of cyclin-dependent protein serine/threonine kinase activity / protein kinase regulator activity / insulin secretion involved in cellular response to glucose stimulus / protein folding chaperone complex / Negative feedback regulation of MAPK pathway / IFNG signaling activates MAPKs / post-transcriptional regulation of gene expression / GP1b-IX-V activation signalling / ERBB2-ERBB3 signaling pathway / Respiratory syncytial virus genome replication / telomerase holoenzyme complex assembly / positive regulation of transforming growth factor beta receptor signaling pathway / Uptake and function of diphtheria toxin / neurotrophin TRK receptor signaling pathway / 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 / pseudopodium / regulation of type I interferon-mediated signaling pathway / TPR domain binding / face development / dendritic growth cone / Assembly and release of respiratory syncytial virus (RSV) virions / regulation of cell differentiation / thyroid gland development / The NLRP3 inflammasome / protein phosphatase activator activity / Sema3A PAK dependent Axon repulsion / somatic stem cell population maintenance / extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of peptidyl-serine phosphorylation / regulation of protein ubiquitination / HSF1-dependent transactivation / MAP kinase kinase kinase activity / response to unfolded protein / HSF1 activation / type II interferon-mediated signaling pathway / axonal growth cone / telomere maintenance via telomerase / negative regulation of protein-containing complex assembly / protein targeting / Attenuation phase / chaperone-mediated protein complex assembly / Schwann cell development / RHOBTB2 GTPase cycle / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / Purinergic signaling in leishmaniasis infection / supramolecular fiber organization / : / heat shock protein binding / DNA polymerase binding / response to muscle stretch / Signaling by ERBB2 / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / myelination / peptide binding / protein folding chaperone / CD209 (DC-SIGN) signaling / cellular response to interleukin-4 / insulin-like growth factor receptor signaling pathway / nitric-oxide synthase regulator activity / placenta development / ESR-mediated signaling / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / Constitutive Signaling by Overexpressed ERBB2 / adenylate cyclase activator activity / thymus development / positive regulation of cell differentiation / Hsp90 protein binding / ATP-dependent protein folding chaperone / wound healing / RAF activation / Signaling by ERBB2 TMD/JMD mutants / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation 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 / C1-like domain superfamily / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / 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 superfamily / Ubiquitin-like domain superfamily / Ribosomal protein S5 domain 2-type fold / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / 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 RAF proto-oncogene serine/threonine-protein kinase / Heat shock protein HSP 90-beta / 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 : 3.16 Å 詳細 データ登録者Mesa P / Garcia-Alonso S / Barbacid M / Montoya G 資金援助 デンマーク, 4件 詳細 詳細を隠すOrganization Grant number 国 Novo Nordisk Foundation NNF14CC0001 デンマーク Novo Nordisk Foundation NNF0024386 デンマーク Novo Nordisk Foundation NNF17SA0030214 デンマーク Novo Nordisk Foundation NNF18OC0055061 デンマーク
引用ジャーナル : Mol Cell / 年 : 2022タイトル : Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation.著者: Sara García-Alonso / Pablo Mesa / Laura de la Puente Ovejero / Gonzalo Aizpurua / Carmen G Lechuga / Eduardo Zarzuela / Clara M Santiveri / Manuel Sanclemente / Javier Muñoz / Mónica ... 著者 : Sara García-Alonso / Pablo Mesa / Laura de la Puente Ovejero / Gonzalo Aizpurua / Carmen G Lechuga / Eduardo Zarzuela / Clara M Santiveri / Manuel Sanclemente / Javier Muñoz / Mónica Musteanu / Ramón Campos-Olivas / Jorge Martínez-Torrecuadrada / Mariano Barbacid / Guillermo Montoya / 要旨 : RAF kinases are RAS-activated enzymes that initiate signaling through the MAPK cascade to control cellular proliferation, differentiation, and survival. Here, we describe the structure of the full- ... RAF kinases are RAS-activated enzymes that initiate signaling through the MAPK cascade to control cellular proliferation, differentiation, and survival. Here, we describe the structure of the full-length RAF1 protein in complex with HSP90 and CDC37 obtained by cryoelectron microscopy. The reconstruction reveals a RAF1 kinase with an unfolded N-lobe separated from its C-lobe. The hydrophobic core of the N-lobe is trapped in the HSP90 dimer, while CDC37 wraps around the chaperone and interacts with the N- and C-lobes of the kinase. The structure indicates how CDC37 can discriminate between the different members of the RAF family. Our structural analysis also reveals that the folded RAF1 assembles with 14-3-3 dimers, suggesting that after folding RAF1 follows a similar activation as B-RAF. Finally, disruption of the interaction between CDC37 and the DFG segment of RAF1 unveils potential vulnerabilities in attempting the pharmacological degradation of RAF1 for therapeutic purposes. 履歴 登録 2022年3月1日 - ヘッダ(付随情報) 公開 2022年9月14日 - マップ公開 2022年9月14日 - 更新 2024年10月9日 - 現状 2024年10月9日 処理サイト : PDBe / 状態 : 公開
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