登録情報 データベース : EMDB / ID : EMD-20578 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of RET/GFRa2/NRTN extracellular complex in the tetrameric form マップデータCryo-EM structure of RET/GFRa2/NRTN extracellular complex in the tetrameric form. 詳細 試料複合体 : RET, GFRAL and GDF15 extracellular complexタンパク質・ペプチド : Neurturinタンパク質・ペプチド : GDNF family receptor alpha-2タンパク質・ペプチド : Proto-oncogene tyrosine-protein kinase receptor Retリガンド : CALCIUM IONリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 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
glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / membrane protein proteolysis ... glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / posterior midgut development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / membrane protein proteolysis / positive regulation of peptidyl-serine phosphorylation of STAT protein / Formation of the ureteric bud / positive regulation of neuron maturation / Formation of the nephric duct / enteric nervous system development / neuron cell-cell adhesion / nerve development / innervation / plasma membrane protein complex / neuron maturation / heparan sulfate binding / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / NCAM1 interactions / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / response to pain / regulation of axonogenesis / extrinsic component of membrane / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of cell size / RET signaling / regulation of cell adhesion / cellular response to retinoic acid / cell surface receptor protein tyrosine kinase signaling pathway / NPAS4 regulates expression of target genes / transmembrane receptor protein tyrosine kinase activity / axon guidance / growth factor activity / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / positive regulation of neuron projection development / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / MAPK cascade / retina development in camera-type eye / nervous system development / signaling receptor activity / RAF/MAP kinase cascade / protein tyrosine kinase activity / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / early endosome / receptor complex / endosome membrane / positive regulation of cell migration / response to xenobiotic stimulus / external side of plasma membrane / axon / protein phosphorylation / signaling receptor binding / neuronal cell body / calcium ion binding / dendrite / positive regulation of gene expression / positive regulation of DNA-templated transcription / signal transduction / extracellular space / extracellular region / ATP binding / plasma membrane 類似検索 - 分子機能 Glial cell line-derived neurotrophic factor receptor alpha 2 / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / Glial cell line-derived neurotrophic factor receptor / GDNF receptor alpha / Glial cell line-derived neurotrophic factor family / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain / Tyrosine-protein kinase, Ret receptor / Tyrosine-protein kinase receptor Ret, cadherin like domain 3 ... Glial cell line-derived neurotrophic factor receptor alpha 2 / Glial cell line-derived neurotrophic factor receptor, alpha 1/2 / Glial cell line-derived neurotrophic factor receptor / GDNF receptor alpha / Glial cell line-derived neurotrophic factor family / GDNF/GAS1 / GDNF/GAS1 domain / GDNF/GAS1 domain / Tyrosine-protein kinase, Ret receptor / Tyrosine-protein kinase receptor Ret, cadherin like domain 3 / Ret, cadherin like domain 1 / RET, cadherin-like domain 4 / RET Cadherin like domain 1 / RET Cadherin like domain 3 / RET Cadherin like domain 4 / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / Cadherin domain / Cadherins domain profile. / Cadherin-like / Cadherin-like superfamily / Cystine-knot cytokine / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, 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 GDNF family receptor alpha-2 / Proto-oncogene tyrosine-protein kinase receptor Ret / Neurturin 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 : 4.3 Å 詳細 データ登録者Li J / Shang GJ / Chen YJ / Brautigam CA / Liou J / Zhang XW / Bai XC 引用ジャーナル : Elife / 年 : 2019タイトル : Cryo-EM analyses reveal the common mechanism and diversification in the activation of RET by different ligands.著者 : Jie Li / Guijun Shang / Yu-Ju Chen / Chad A Brautigam / Jen Liou / Xuewu Zhang / Xiao-Chen Bai / 要旨 : RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ... RET is a receptor tyrosine kinase (RTK) that plays essential roles in development and has been implicated in several human diseases. Different from most of RTKs, RET requires not only its cognate ligands but also co-receptors for activation, the mechanisms of which remain unclear due to lack of high-resolution structures of the ligand/co-receptor/receptor complexes. Here, we report cryo-EM structures of the extracellular region ternary complexes of GDF15/GFRAL/RET, GDNF/GFRα1/RET, NRTN/GFRα2/RET and ARTN/GFRα3/RET. These structures reveal that all the four ligand/co-receptor pairs, while using different atomic interactions, induce a specific dimerization mode of RET that is poised to bring the two kinase domains into close proximity for cross-phosphorylation. The NRTN/GFRα2/RET dimeric complex further pack into a tetrameric assembly, which is shown by our cell-based assays to regulate the endocytosis of RET. Our analyses therefore reveal both the common mechanism and diversification in the activation of RET by different ligands. 履歴 登録 2019年8月8日 - ヘッダ(付随情報) 公開 2019年10月2日 - マップ公開 2019年10月2日 - 更新 2020年7月29日 - 現状 2020年7月29日 処理サイト : RCSB / 状態 : 公開
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