登録情報 データベース : EMDB / ID : EMD-23929 構造の表示 ダウンロードとリンクタイトル Autoinhibited neurofibrobmin マップデータ 詳細 試料複合体 : Neurofibrominタンパク質・ペプチド : Isoform I of Neurofibromin 詳細 キーワード scaffold / RAS-GAP / HEAT repeat / autoinhibition / tumour suppressor / ANTITUMOR 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
positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process / gamma-aminobutyric acid secretion, neurotransmission ... positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process / gamma-aminobutyric acid secretion, neurotransmission / negative regulation of mast cell proliferation / Schwann cell proliferation / vascular associated smooth muscle cell proliferation / mast cell proliferation / glutamate secretion, neurotransmission / negative regulation of Schwann cell proliferation / negative regulation of leukocyte migration / negative regulation of vascular associated smooth muscle cell migration / positive regulation of adenylate cyclase activity / regulation of cell-matrix adhesion / forebrain morphogenesis / negative regulation of neurotransmitter secretion / hair follicle maturation / cell communication / regulation of blood vessel endothelial cell migration / smooth muscle tissue development / camera-type eye morphogenesis / negative regulation of oligodendrocyte differentiation / sympathetic nervous system development / myelination in peripheral nervous system / myeloid leukocyte migration / peripheral nervous system development / phosphatidylcholine binding / phosphatidylethanolamine binding / metanephros development / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / negative regulation of Ras protein signal transduction / collagen fibril organization / regulation of bone resorption / regulation of long-term synaptic potentiation / neural tube development / forebrain astrocyte development / endothelial cell proliferation / artery morphogenesis / regulation of postsynapse organization / pigmentation / regulation of synaptic transmission, GABAergic / negative regulation of neuroblast proliferation / negative regulation of MAPK cascade / adrenal gland development / negative regulation of protein import into nucleus / negative regulation of cell-matrix adhesion / spinal cord development / regulation of GTPase activity / Rac protein signal transduction / oligodendrocyte differentiation / negative regulation of osteoclast differentiation / negative regulation of endothelial cell proliferation / RAS signaling downstream of NF1 loss-of-function variants / negative regulation of astrocyte differentiation / extrinsic apoptotic signaling pathway via death domain receptors / neuroblast proliferation / regulation of angiogenesis / Schwann cell development / negative regulation of stem cell proliferation / negative regulation of fibroblast proliferation / skeletal muscle tissue development / extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of endothelial cell proliferation / negative regulation of angiogenesis / negative regulation of cell migration / extracellular matrix organization / osteoclast differentiation / GTPase activator activity / phosphatidylinositol 3-kinase/protein kinase B signal transduction / regulation of ERK1 and ERK2 cascade / positive regulation of GTPase activity / negative regulation of MAP kinase activity / liver development / stem cell proliferation / long-term synaptic potentiation / regulation of long-term neuronal synaptic plasticity / negative regulation of protein kinase activity / wound healing / visual learning / brain development / cerebral cortex development / cognition / osteoblast differentiation / Regulation of RAS by GAPs / protein import into nucleus / MAPK cascade / positive regulation of neuron apoptotic process / presynapse / heart development / cellular response to heat / fibroblast proliferation / actin cytoskeleton organization / regulation of gene expression 類似検索 - 分子機能 Ras GTPase-activating protein / Ras GTPase-activating protein, conserved site / Ras GTPase-activating proteins domain signature. / GTPase-activator protein for Ras-like GTPase / Ras GTPase-activating proteins profile. / GTPase-activator protein for Ras-like GTPases / Ras GTPase-activating domain / Divergent CRAL/TRIO domain / CRAL-TRIO lipid binding domain profile. / Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) ... Ras GTPase-activating protein / Ras GTPase-activating protein, conserved site / Ras GTPase-activating proteins domain signature. / GTPase-activator protein for Ras-like GTPase / Ras GTPase-activating proteins profile. / GTPase-activator protein for Ras-like GTPases / Ras GTPase-activating domain / Divergent CRAL/TRIO domain / CRAL-TRIO lipid binding domain profile. / Domain in homologues of a S. cerevisiae phosphatidylinositol transfer protein (Sec14p) / CRAL-TRIO lipid binding domain / CRAL-TRIO lipid binding domain superfamily / Rho GTPase activation protein / PH-like domain superfamily / Armadillo-type fold 類似検索 - ドメイン・相同性生物種 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 : 5.6 Å 詳細 データ登録者Lupton CJ / Bayly-Jones C 資金援助 オーストラリア, 1件 詳細 詳細を隠すOrganization Grant number 国 Not funded オーストラリア
引用ジャーナル : Nat Struct Mol Biol / 年 : 2021タイトル : The cryo-EM structure of the human neurofibromin dimer reveals the molecular basis for neurofibromatosis type 1.著者 : Christopher J Lupton / Charles Bayly-Jones / Laura D'Andrea / Cheng Huang / Ralf B Schittenhelm / Hari Venugopal / James C Whisstock / Michelle L Halls / Andrew M Ellisdon / 要旨 : Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase- ... Neurofibromin (NF1) mutations cause neurofibromatosis type 1 and drive numerous cancers, including breast and brain tumors. NF1 inhibits cellular proliferation through its guanosine triphosphatase-activating protein (GAP) activity against rat sarcoma (RAS). In the present study, cryo-electron microscope studies reveal that the human ~640-kDa NF1 homodimer features a gigantic 30 × 10 nm array of α-helices that form a core lemniscate-shaped scaffold. Three-dimensional variability analysis captured the catalytic GAP-related domain and lipid-binding SEC-PH domains positioned against the core scaffold in a closed, autoinhibited conformation. We postulate that interaction with the plasma membrane may release the closed conformation to promote RAS inactivation. Our structural data further allow us to map the location of disease-associated NF1 variants and provide a long-sought-after structural explanation for the extreme susceptibility of the molecule to loss-of-function mutations. Collectively these findings present potential new routes for therapeutic modulation of the RAS pathway. 履歴 登録 2021年5月4日 - ヘッダ(付随情報) 公開 2021年12月15日 - マップ公開 2021年12月15日 - 更新 2024年5月29日 - 現状 2024年5月29日 処理サイト : RCSB / 状態 : 公開
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