登録情報 データベース : EMDB / ID : EMD-23813 構造の表示 ダウンロードとリンクタイトル Autoinhibited B-Raf:(14-3-3)2:MEK complex with resolved RBD マップデータ 詳細 試料複合体 : Autoinhibited B-Raf:(14-3-3)2:MEK complex with resolved RBD複合体 : B-rafタンパク質・ペプチド : Serine/threonine-protein kinase B-raf複合体 : MEKタンパク質・ペプチド : Dual specificity mitogen-activated protein kinase kinase 1複合体 : 14-3-3 protein zeta/deltaタンパク質・ペプチド : 14-3-3 protein zeta/deltaリガンド : ZINC IONリガンド : N-(3-fluoro-4-{[4-methyl-2-oxo-7-(pyrimidin-2-yloxy)-2H-chromen-3-yl]methyl}pyridin-2-yl)-N'-methylsulfuric diamide 詳細 キーワード B-Raf / MEK / 14-3-3 / B-Raf complex / B-Raf monomer / Inactive B-Raf / Serine/threonine-protein kinase B-raf / RBD / signaling protein / SIGNALING PROTEIN-TRANSFERASE complex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
epithelial cell proliferation involved in lung morphogenesis / synaptic target recognition / positive regulation of endodermal cell differentiation / Golgi reassembly / JUN kinase kinase activity / CD4-positive, alpha-beta T cell differentiation / regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / mitogen-activated protein kinase kinase / establishment of Golgi localization ... epithelial cell proliferation involved in lung morphogenesis / synaptic target recognition / positive regulation of endodermal cell differentiation / Golgi reassembly / JUN kinase kinase activity / CD4-positive, alpha-beta T cell differentiation / regulation of axon regeneration / NOTCH4 Activation and Transmission of Signal to the Nucleus / mitogen-activated protein kinase kinase / establishment of Golgi localization / placenta blood vessel development / MAP-kinase scaffold activity / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / labyrinthine layer development / negative regulation of synaptic vesicle exocytosis / cerebellar cortex formation / type B pancreatic cell proliferation / Signalling to p38 via RIT and RIN / respiratory system process / myeloid progenitor cell differentiation / head morphogenesis / ARMS-mediated activation / tube formation / endothelial cell apoptotic process / regulation of synapse maturation / Signaling by MAP2K mutants / SHOC2 M1731 mutant abolishes MRAS complex function / Gain-of-function MRAS complexes activate RAF signaling / Rap1 signalling / negative regulation of fibroblast migration / positive regulation of D-glucose transmembrane transport / establishment of protein localization to membrane / positive regulation of axonogenesis / negative regulation of protein localization to nucleus / regulation of Golgi inheritance / regulation of T cell differentiation / trachea formation / mitogen-activated protein kinase kinase binding / Negative feedback regulation of MAPK pathway / regulation of early endosome to late endosome transport / KSRP (KHSRP) binds and destabilizes mRNA / regulation of stress-activated MAPK cascade / MAPK3 (ERK1) activation / GP1b-IX-V activation signalling / Frs2-mediated activation / positive regulation of axon regeneration / ERBB2-ERBB3 signaling pathway / stress fiber assembly / endodermal cell differentiation / face development / MAP kinase kinase activity / Bergmann glial cell differentiation / synaptic vesicle exocytosis / Uptake and function of anthrax toxins / thyroid gland development / Regulation of localization of FOXO transcription factors / somatic stem cell population maintenance / protein kinase activator activity / Interleukin-3, Interleukin-5 and GM-CSF signaling / phosphoserine residue binding / MAP kinase kinase kinase activity / Activation of BAD and translocation to mitochondria / positive regulation of protein serine/threonine kinase activity / postsynaptic modulation of chemical synaptic transmission / negative regulation of endothelial cell apoptotic process / protein targeting / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Schwann cell development / regulation of ERK1 and ERK2 cascade / cellular response to glucose starvation / keratinocyte differentiation / response to cAMP / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / positive regulation of peptidyl-serine phosphorylation / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / positive regulation of substrate adhesion-dependent cell spreading / myelination / ERK1 and ERK2 cascade / Transcriptional and post-translational regulation of MITF-M expression and activity / protein serine/threonine/tyrosine kinase activity / substrate adhesion-dependent cell spreading / protein sequestering activity / insulin-like growth factor receptor signaling pathway / cellular response to calcium ion / negative regulation of innate immune response / hippocampal mossy fiber to CA3 synapse / protein serine/threonine kinase activator activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / thymus development / animal organ morphogenesis / Signal transduction by L1 / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / cell motility / Deactivation of the beta-catenin transactivating complex / lung development / RAF activation 類似検索 - 分子機能 : / 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. ... : / 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 / 14-3-3 proteins signature 2. / 14-3-3 protein, conserved site / 14-3-3 proteins signature 1. / 14-3-3 protein / 14-3-3 homologues / 14-3-3 domain / 14-3-3 domain superfamily / 14-3-3 protein / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / 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 Serine/threonine-protein kinase B-raf / 14-3-3 protein zeta/delta / Dual specificity mitogen-activated protein kinase kinase 1 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 : 3.66 Å 詳細 データ登録者Martinez Fiesco JA / Ping Z 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Cancer Institute (NIH/NCI) ZIA BC 011744 米国 National Institutes of Health/National Cancer Institute (NIH/NCI) ZIA BC 010329 米国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Structural insights into the BRAF monomer-to-dimer transition mediated by RAS binding.著者 : Juliana A Martinez Fiesco / David E Durrant / Deborah K Morrison / Ping Zhang / 要旨 : RAF kinases are essential effectors of RAS, but how RAS binding initiates the conformational changes needed for autoinhibited RAF monomers to form active dimers has remained unclear. Here, we present ... RAF kinases are essential effectors of RAS, but how RAS binding initiates the conformational changes needed for autoinhibited RAF monomers to form active dimers has remained unclear. Here, we present cryo-electron microscopy structures of full-length BRAF complexes derived from mammalian cells: autoinhibited, monomeric BRAF:14-3-3:MEK and BRAF:14-3-3 complexes, and an inhibitor-bound, dimeric BRAF:14-3-3 complex, at 3.7, 4.1, and 3.9 Å resolution, respectively. In both autoinhibited, monomeric structures, the RAS binding domain (RBD) of BRAF is resolved, revealing that the RBD forms an extensive contact interface with the 14-3-3 protomer bound to the BRAF C-terminal site and that key basic residues required for RBD-RAS binding are exposed. Moreover, through structure-guided mutational studies, our findings indicate that RAS-RAF binding is a dynamic process and that RBD residues at the center of the RBD:14-3-3 interface have a dual function, first contributing to RAF autoinhibition and then to the full spectrum of RAS-RBD interactions. 履歴 登録 2021年4月9日 - ヘッダ(付随情報) 公開 2022年1月26日 - マップ公開 2022年1月26日 - 更新 2025年5月28日 - 現状 2025年5月28日 処理サイト : RCSB / 状態 : 公開
すべて表示 表示を減らす