登録情報 データベース : PDB / ID : 7mp6 構造の表示 ダウンロードとリンクタイトル Neurofibromin homodimer 要素Isoform I of Neurofibromin 詳細 キーワード ANTITUMOR PROTEIN / tumor supressor / HEAT repeat / Ras-GAP / scaffold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 / gamma-aminobutyric acid secretion, neurotransmission / negative regulation of mast cell proliferation ... 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 / gamma-aminobutyric acid secretion, neurotransmission / negative regulation of mast cell proliferation / mast cell apoptotic process / 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 / hair follicle maturation / negative regulation of neurotransmitter secretion / 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 / peripheral nervous system development / myelination in peripheral nervous system / myeloid leukocyte migration / 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 / endothelial cell proliferation / forebrain astrocyte development / artery morphogenesis / regulation of postsynapse organization / regulation of synaptic transmission, GABAergic / negative regulation of neuroblast proliferation / adrenal gland development / negative regulation of protein import into nucleus / negative regulation of MAPK cascade / negative regulation of cell-matrix adhesion / pigmentation / regulation of GTPase activity / spinal cord development / 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 / regulation of ERK1 and ERK2 cascade / Schwann cell development / negative regulation of angiogenesis / negative regulation of stem cell proliferation / negative regulation of fibroblast proliferation / extrinsic apoptotic signaling pathway in absence of ligand / skeletal muscle tissue development / negative regulation of MAP kinase activity / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of endothelial cell proliferation / phosphatidylinositol 3-kinase/protein kinase B signal transduction / GTPase activator activity / osteoclast differentiation / extracellular matrix organization / positive regulation of GTPase activity / liver development / negative regulation of cell migration / stem cell proliferation / long-term synaptic potentiation / negative regulation of protein kinase activity / regulation of long-term neuronal synaptic plasticity / wound healing / visual learning / brain development / cerebral cortex development / cognition / Regulation of RAS by GAPs / osteoblast differentiation / protein import into nucleus / positive regulation of neuron apoptotic process / MAPK cascade / presynapse / regulation of gene expression / heart development / cellular response to heat / fibroblast proliferation / actin cytoskeleton organization 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 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 6.25 Å 詳細データ登録者 Lupton, C.J. / Bayly-Jones, C. / Ellisdon, A.M. 資金援助 オーストラリア, 1件 詳細 詳細を隠す組織 認可番号 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 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2021年12月15日 Provider : repository / タイプ : Initial release改定 1.1 2021年12月29日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID / _citation_author.name 改定 1.2 2022年3月16日 Group : Structure summary / カテゴリ : audit_author改定 1.3 2024年5月29日 Group : Data collection / カテゴリ : chem_comp_atom / chem_comp_bond
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