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
synaptic target recognition / negative regulation of homotypic cell-cell adhesion / epithelial cell proliferation involved in lung morphogenesis / Golgi reassembly / positive regulation of endodermal cell differentiation / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / regulation of vascular associated smooth muscle contraction / CD4-positive, alpha-beta T cell differentiation / NOTCH4 Activation and Transmission of Signal to the Nucleus / positive regulation of axon regeneration ... synaptic target recognition / negative regulation of homotypic cell-cell adhesion / epithelial cell proliferation involved in lung morphogenesis / Golgi reassembly / positive regulation of endodermal cell differentiation / negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway / regulation of vascular associated smooth muscle contraction / CD4-positive, alpha-beta T cell differentiation / NOTCH4 Activation and Transmission of Signal to the Nucleus / positive regulation of axon regeneration / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative regulation of synaptic vesicle exocytosis / mitogen-activated protein kinase kinase / establishment of Golgi localization / positive regulation of muscle contraction / Golgi inheritance / placenta blood vessel development / Signalling to p38 via RIT and RIN / MAP kinase scaffold activity / regulation of axon regeneration / respiratory system process / cerebellar cortex formation / labyrinthine layer development / head morphogenesis / ARMS-mediated activation / myeloid progenitor cell differentiation / tube formation / melanosome transport / 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 / negative regulation of fibroblast migration / positive regulation of D-glucose transmembrane transport / Rap1 signalling / establishment of protein localization to membrane / type B pancreatic cell proliferation / central nervous system neuron differentiation / vesicle transport along microtubule / positive regulation of Ras protein signal transduction / regulation of Golgi inheritance / mitogen-activated protein kinase kinase kinase binding / regulation of T cell differentiation / positive regulation of axonogenesis / trachea formation / negative regulation of protein localization to nucleus / KSRP (KHSRP) binds and destabilizes mRNA / triglyceride homeostasis / regulation of early endosome to late endosome transport / Negative feedback regulation of MAPK pathway / regulation of stress-activated MAPK cascade / GP1b-IX-V activation signalling / Frs2-mediated activation / stress fiber assembly / MAPK3 (ERK1) activation / ERBB2-ERBB3 signaling pathway / face development / endodermal cell differentiation / MAP kinase kinase activity / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / Bergmann glial cell differentiation / positive regulation of protein serine/threonine kinase activity / thyroid gland development / positive regulation of ATP biosynthetic process / Regulation of localization of FOXO transcription factors / Interleukin-3, Interleukin-5 and GM-CSF signaling / Uptake and function of anthrax toxins / somatic stem cell population maintenance / positive regulation of peptidyl-serine phosphorylation / synaptic vesicle exocytosis / Activation of BAD and translocation to mitochondria / phosphoserine residue binding / MAP kinase kinase kinase activity / protein kinase activator activity / negative regulation of endothelial cell apoptotic process / regulation of ERK1 and ERK2 cascade / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / Schwann cell development / response to axon injury / postsynaptic modulation of chemical synaptic transmission / protein targeting / cellular response to glucose starvation / keratinocyte differentiation / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / RHO GTPases activate PKNs / Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex / neuron projection morphogenesis / ERK1 and ERK2 cascade / positive regulation of stress fiber assembly / negative regulation of TORC1 signaling / myelination / positive regulation of substrate adhesion-dependent cell spreading / protein serine/threonine/tyrosine kinase activity / Transcriptional and post-translational regulation of MITF-M expression and activity / substrate adhesion-dependent cell spreading / insulin-like growth factor receptor signaling pathway / lung development / positive regulation of autophagy / cellular response to calcium ion 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 / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / 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
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