登録情報 データベース : EMDB / ID : EMD-0026 ダウンロードとリンクタイトル Neurturin-GFRa2-RET extracellular complex マップデータConsensus refinement with C2 symmetry applied. 詳細 試料複合体 : Neurturin-GFRa2-RET extracellular complex複合体 : Neurturin複合体 : GDNF family receptor alpha-2タンパク質・ペプチド : GDNF family receptor alpha-2複合体 : Proto-oncogene tyrosine-protein kinase receptor Retタンパク質・ペプチド : Proto-oncogene tyrosine-protein kinase receptor Ret 詳細 キーワード Neurotrophic signalling / Receptor tyrosine kinase / GDNF family of ligands / SIGNALING PROTEIN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 / GDF15-GFRAL signaling pathway / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / posterior midgut development ... glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / GDF15-GFRAL signaling pathway / Peyer's patch morphogenesis / positive regulation of metanephric glomerulus development / ureter maturation / embryonic epithelial tube formation / glial cell-derived neurotrophic factor receptor signaling pathway / lymphocyte migration into lymphoid organs / posterior midgut development / positive regulation of peptidyl-serine phosphorylation of STAT protein / membrane protein proteolysis / Formation of the ureteric bud / positive regulation of neuron maturation / neuron cell-cell adhesion / Formation of the nephric duct / enteric nervous system development / nerve development / innervation / plasma membrane protein complex / neuron maturation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / heparan sulfate binding / NCAM1 interactions / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / extrinsic component of membrane / regulation of axonogenesis / response to pain / homophilic cell adhesion via plasma membrane adhesion molecules / RET signaling / positive regulation of cell size / regulation of cell adhesion / cell surface receptor protein tyrosine kinase signaling pathway / cellular response to retinoic acid / 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 / MAPK cascade / neuron projection development / signaling receptor activity / retina development in camera-type eye / nervous system development / 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 / protein phosphorylation / axon / external side of plasma membrane / signaling receptor binding / neuronal cell body / dendrite / calcium ion binding / 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 / RET, Cysteine Rich Domain / Transforming growth factor-beta, C-terminal / Transforming growth factor beta like domain / TGF-beta family profile. / Cadherin domain / Cadherin-like / Cadherins domain profile. / 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 / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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 : 6.3 Å 詳細 データ登録者Bigalke JM / Aibara S 資金援助 スウェーデン, 2件 詳細 詳細を隠すOrganization Grant number 国 Knut and Alice Wallenberg Foundation スウェーデン Swedish Research Council NT_2015-04107 スウェーデン
引用ジャーナル : Sci Adv / 年 : 2019タイトル : Cryo-EM structure of the activated RET signaling complex reveals the importance of its cysteine-rich domain.著者 : Janna M Bigalke / Shintaro Aibara / Robert Roth / Göran Dahl / Euan Gordon / Sarah Dorbéus / A Amunts / Jenny Sandmark / 要旨 : Signaling through the receptor tyrosine kinase RET is essential during normal development. Both gain- and loss-of-function mutations are involved in a variety of diseases, yet the molecular details ... Signaling through the receptor tyrosine kinase RET is essential during normal development. Both gain- and loss-of-function mutations are involved in a variety of diseases, yet the molecular details of receptor activation have remained elusive. We have reconstituted the complete extracellular region of the RET signaling complex together with Neurturin (NRTN) and GFRα2 and determined its structure at 5.7-Å resolution by cryo-EM. The proteins form an assembly through RET-GFRα2 and RET-NRTN interfaces. Two key interaction points required for RET extracellular domain binding were observed: (i) the calcium-binding site in RET that contacts GFRα2 domain 3 and (ii) the RET cysteine-rich domain interaction with NRTN. The structure highlights the importance of the RET cysteine-rich domain and allows proposition of a model to explain how complex formation leads to RET receptor dimerization and its activation. This provides a framework for targeting RET activity and for further exploration of mechanisms underlying neurological diseases. 履歴 登録 2018年5月23日 - ヘッダ(付随情報) 公開 2018年8月22日 - マップ公開 2019年8月14日 - 更新 2024年11月20日 - 現状 2024年11月20日 処理サイト : PDBe / 状態 : 公開
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