登録情報 データベース : EMDB / ID : EMD-23921 構造の表示 ダウンロードとリンクタイトル Cryo-EM map of the c-MET II/HGF I/HGF II (K4 and SPH) sub-complex マップデータCryo-EM map of the c-MET II/HGF I/HGF II sub-complex. Only K4 and SPH domains are present in HGF II. 詳細 試料複合体 : c-MET II/HGF I/HGF II (K4 and SPH) sub-complexタンパク質・ペプチド : Hepatocyte growth factorタンパク質・ペプチド : Hepatocyte growth factor receptor 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
regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins ... regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / negative regulation of guanyl-nucleotide exchange factor activity / hepatocyte growth factor receptor activity / Drug-mediated inhibition of MET activation / skeletal muscle cell proliferation / endothelial cell morphogenesis / MET activates STAT3 / negative regulation of hydrogen peroxide-mediated programmed cell death / MET interacts with TNS proteins / MET Receptor Activation / semaphorin-plexin signaling pathway involved in axon guidance / hepatocyte growth factor receptor signaling pathway / semaphorin receptor activity / MET receptor recycling / semaphorin receptor complex / pancreas development / MET activates PTPN11 / MET activates RAP1 and RAC1 / myoblast proliferation / Sema4D mediated inhibition of cell attachment and migration / MET activates PI3K/AKT signaling / negative regulation of stress fiber assembly / positive regulation of endothelial cell chemotaxis / negative regulation of Rho protein signal transduction / MET activates PTK2 signaling / cellular response to hepatocyte growth factor stimulus / positive regulation of DNA biosynthetic process / branching morphogenesis of an epithelial tube / positive chemotaxis / negative regulation of thrombin-activated receptor signaling pathway / chemoattractant activity / negative regulation of release of cytochrome c from mitochondria / negative regulation of peptidyl-serine phosphorylation / negative regulation of interleukin-6 production / positive regulation of interleukin-10 production / semaphorin-plexin signaling pathway / epithelial to mesenchymal transition / establishment of skin barrier / positive regulation of osteoblast differentiation / MET activates RAS signaling / phagocytosis / MECP2 regulates neuronal receptors and channels / negative regulation of extrinsic apoptotic signaling pathway via death domain receptors / positive regulation of microtubule polymerization / Interleukin-7 signaling / negative regulation of autophagy / basal plasma membrane / cell chemotaxis / InlB-mediated entry of Listeria monocytogenes into host cell / platelet alpha granule lumen / liver development / epithelial cell proliferation / molecular function activator activity / growth factor activity / cell morphogenesis / neuron differentiation / Negative regulation of MET activity / receptor protein-tyrosine kinase / negative regulation of inflammatory response / Constitutive Signaling by Aberrant PI3K in Cancer / cell migration / Platelet degranulation / PIP3 activates AKT signaling / nervous system development / mitotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / RAF/MAP kinase cascade / protein phosphatase binding / protein tyrosine kinase activity / Interleukin-4 and Interleukin-13 signaling / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / receptor complex / positive regulation of cell migration / positive regulation of protein phosphorylation / phosphorylation / signaling receptor binding / negative regulation of apoptotic process / cell surface / signal transduction / positive regulation of transcription by RNA polymerase II / extracellular space / extracellular region / ATP binding / identical protein binding / membrane / plasma membrane 類似検索 - 分子機能 Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / divergent subfamily of APPLE domains / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain ... Hepatocyte growth factor / Hepatocyte growth factor/Macrophage stimulatory protein / divergent subfamily of APPLE domains / Tyrosine-protein kinase, HGF/MSP receptor / Plexin family / Plexin repeat / Plexin repeat / Sema domain / semaphorin domain / Sema domain / Sema domain superfamily / Sema domain profile. / PAN/Apple domain profile. / PAN domain / PAN/Apple domain / IPT/TIG domain / ig-like, plexins, transcription factors / PSI domain / domain found in Plexins, Semaphorins and Integrins / IPT domain / Kringle domain / Kringle / Kringle, conserved site / Kringle superfamily / Kringle domain signature. / Kringle domain profile. / Kringle domain / Kringle-like fold / Peptidase S1A, chymotrypsin family / Serine proteases, trypsin domain profile. / Trypsin-like serine protease / Serine proteases, trypsin domain / Trypsin / Immunoglobulin E-set / 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 / WD40/YVTN repeat-like-containing domain superfamily / Peptidase S1, PA clan, chymotrypsin-like fold / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Peptidase S1, PA clan / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 Hepatocyte growth factor receptor / Hepatocyte growth factor 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 : 4.0 Å 詳細 データ登録者Uchikawa E / Chen ZM / Xiao GY / Zhang XW / Bai XC 引用ジャーナル : Nat Commun / 年 : 2021タイトル : Structural basis of the activation of c-MET receptor.著者 : Emiko Uchikawa / Zhiming Chen / Guan-Yu Xiao / Xuewu Zhang / Xiao-Chen Bai / 要旨 : The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic ... The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor. 履歴 登録 2021年5月1日 - ヘッダ(付随情報) 公開 2021年6月9日 - マップ公開 2021年6月9日 - 更新 2021年7月28日 - 現状 2021年7月28日 処理サイト : RCSB / 状態 : 公開
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