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基本情報
登録情報 | データベース: PDB / ID: 4ux8 | |||||||||
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タイトル | RET recognition of GDNF-GFRalpha1 ligand by a composite binding site promotes membrane-proximal self-association | |||||||||
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![]() | SIGNALING PROTEIN / VERTEBRATE DEVELOPMENT / HUMAN DISEASES / PART OF THE RET-GFL- GFRA COMPLEX | |||||||||
機能・相同性 | ![]() chemoattractant activity involved in axon guidance / postsynaptic membrane organization / mesenchymal to epithelial transition involved in metanephros morphogenesis / dorsal spinal cord development / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / ureteric bud formation / positive regulation of ureteric bud formation / regulation of semaphorin-plexin signaling pathway / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity ...chemoattractant activity involved in axon guidance / postsynaptic membrane organization / mesenchymal to epithelial transition involved in metanephros morphogenesis / dorsal spinal cord development / positive regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis / ureteric bud formation / positive regulation of ureteric bud formation / regulation of semaphorin-plexin signaling pathway / postganglionic parasympathetic fiber development / positive regulation of monooxygenase activity / glial cell-derived neurotrophic factor receptor activity / glial cell-derived neurotrophic factor receptor binding / RET signaling / 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 / : / regulation of morphogenesis of a branching structure / regulation of dopamine uptake involved in synaptic transmission / membrane protein proteolysis / neurotrophin receptor activity / 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 / peristalsis / positive regulation of branching involved in ureteric bud morphogenesis / positive regulation of dopamine secretion / sympathetic nervous system development / innervation / peripheral nervous system development / organ induction / regulation of stem cell differentiation / plasma membrane protein complex / metanephros development / commissural neuron axon guidance / neuron maturation / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / NCAM1 interactions / mRNA stabilization / RAF/MAP kinase cascade / positive regulation of cell adhesion mediated by integrin / neural crest cell migration / ureteric bud development / branching involved in ureteric bud morphogenesis / response to pain / regulation of axonogenesis / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of cell size / RET signaling / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / embryonic organ development / regulation of cell adhesion / cellular response to retinoic acid / NPAS4 regulates expression of target genes / transmembrane receptor protein tyrosine kinase activity / multivesicular body / adult locomotory behavior / kidney development / positive regulation of cell differentiation / axon guidance / growth factor activity / neuron differentiation / receptor protein-tyrosine kinase / receptor tyrosine kinase binding / positive regulation of neuron projection development / activation of cysteine-type endopeptidase activity involved in apoptotic process / male gonad development / neuron projection development / positive regulation of peptidyl-tyrosine phosphorylation / MAPK cascade / cell migration / integrin binding / retina development in camera-type eye / nervous system development / signaling receptor activity / RAF/MAP kinase cascade / regulation of gene expression / protein tyrosine kinase activity / negative regulation of neuron apoptotic process / 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 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / ネガティブ染色法 / 解像度: 24 Å | |||||||||
![]() | Goodman, K. / Kjaer, S. / Beuron, F. / Knowles, P. / Nawrotek, A. / Burns, E. / Purkiss, A. / George, R. / Santoro, M. / Morris, E.P. / McDonald, N.Q. | |||||||||
![]() | ![]() タイトル: RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association. 著者: Kerry M Goodman / Svend Kjær / Fabienne Beuron / Phillip P Knowles / Agata Nawrotek / Emily M Burns / Andrew G Purkiss / Roger George / Massimo Santoro / Edward P Morris / Neil Q McDonald / ![]() ![]() 要旨: The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a ...The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting in RET transmembrane signaling. We present a hybrid structural model, derived from electron microscopy (EM) and low-angle X-ray scattering (SAXS) data, of the RET extracellular domain (RET(ECD)), GDNF, and GFRα1 ternary complex, defining the basis for ligand recognition. RET(ECD) envelopes the dimeric ligand complex through a composite binding site comprising four discrete contact sites. The GFRα1-mediated contacts are crucial, particularly close to the invariant RET calcium-binding site, whereas few direct contacts are made by GDNF, explaining how distinct ligand/coreceptor pairs are accommodated. The RET(ECD) cysteine-rich domain (CRD) contacts both ligand components and makes homotypic membrane-proximal interactions occluding three different antibody epitopes. Coupling of these CRD-mediated interactions suggests models for ligand-induced RET activation and ligand-independent oncogenic deregulation. | |||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 334.4 KB | 表示 | ![]() |
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PDB形式 | ![]() | 258.5 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 865.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1005 KB | 表示 | |
XML形式データ | ![]() | 65.3 KB | 表示 | |
CIF形式データ | ![]() | 96.2 KB | 表示 | |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 67922.539 Da / 分子数: 2 / 断片: RET EXTRACELLULAR DOMAIN, RESIDUES 29-635 / 変異: YES / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P07949, receptor protein-tyrosine kinase #2: タンパク質 | 分子量: 51091.277 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() ![]() 参照: UniProt: O35748, UniProt: Q62997*PLUS #3: タンパク質 | 分子量: 15096.242 Da / 分子数: 2 / 断片: MATURE, UNP RESIDUES 78-211 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #4: 多糖 | #5: 化合物 | ChemComp-CA / 配列の詳細 | RESIDUES 509 TO 635 ARE NOT IN THE MODEL | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Reconstituted mammalian RETecd-GDNF-GFRa1 ternary complex タイプ: COMPLEX |
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緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: YES / 凍結: NO |
染色 | タイプ: NEGATIVE / 染色剤: uranyl acetate |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Tecnai F20 / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TECNAI F20 / 日付: 2012年11月8日 |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: OTHER / 倍率(公称値): 80000 X / 最小 デフォーカス(公称値): 900 nm |
撮影 | 電子線照射量: 100 e/Å2 フィルム・検出器のモデル: TVIPS TEMCAM-F415 (4k x 4k) |
画像スキャン | デジタル画像の数: 1200 |
放射波長 | 相対比: 1 |
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解析
EMソフトウェア |
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対称性 | 点対称性: C2 (2回回転対称) | ||||||||||||
3次元再構成 | 手法: ANGULAR RECONSTITUTION / 解像度: 24 Å / 粒子像の数: 8519 詳細: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-2712. (DEPOSITION ID: 12696). 対称性のタイプ: POINT | ||||||||||||
精密化 | 最高解像度: 24 Å | ||||||||||||
精密化ステップ | サイクル: LAST / 最高解像度: 24 Å
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