+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-13398 | ||||||||||||
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タイトル | The core region of human Neurofibromin Isoform 2 stabilized by Zinc. | ||||||||||||
マップデータ | |||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / gamma-aminobutyric acid secretion, neurotransmission / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process ...positive regulation of mast cell apoptotic process / negative regulation of Rac protein signal transduction / regulation of glial cell differentiation / gamma-aminobutyric acid secretion, neurotransmission / observational learning / Schwann cell migration / negative regulation of Schwann cell migration / vascular associated smooth muscle cell migration / amygdala development / mast cell apoptotic process / 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 / regulation of blood vessel endothelial cell migration / cell communication / smooth muscle tissue development / negative regulation of oligodendrocyte differentiation / camera-type eye morphogenesis / sympathetic nervous system development / myelination in peripheral nervous system / myeloid leukocyte migration / phosphatidylethanolamine binding / phosphatidylcholine binding / peripheral nervous system development / metanephros development / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / collagen fibril organization / endothelial cell proliferation / regulation of bone resorption / regulation of long-term synaptic potentiation / neural tube development / forebrain astrocyte development / regulation of postsynapse organization / 顔料 / artery morphogenesis / negative regulation of neuroblast proliferation / regulation of synaptic transmission, GABAergic / adrenal gland development / negative regulation of protein import into nucleus / negative regulation of cell-matrix adhesion / spinal cord development / regulation of GTPase activity / negative regulation of MAPK cascade / 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 / neuroblast proliferation / extrinsic apoptotic signaling pathway via death domain receptors / 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 / GTPase activator activity / extracellular matrix organization / negative regulation of angiogenesis / osteoclast differentiation / regulation of ERK1 and ERK2 cascade / negative regulation of cell migration / liver development / negative regulation of MAP kinase activity / phosphatidylinositol 3-kinase/protein kinase B signal transduction / long-term synaptic potentiation / stem cell proliferation / regulation of long-term neuronal synaptic plasticity / brain development / negative regulation of protein kinase activity / visual learning / wound healing / cerebral cortex development / 認識 / osteoblast differentiation / positive regulation of GTPase activity / Regulation of RAS by GAPs / protein import into nucleus / positive regulation of neuron apoptotic process / 分裂促進因子活性化タンパク質キナーゼ / presynapse / cellular response to heat / heart development / fibroblast proliferation / actin cytoskeleton organization / 遺伝子発現の調節 / 血管新生 類似検索 - 分子機能 | ||||||||||||
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: 3.1 Å | ||||||||||||
データ登録者 | Naschberger A / Baradaran R / Carroni M / Rupp B | ||||||||||||
資金援助 | オーストリア, 3件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: The structure of neurofibromin isoform 2 reveals different functional states. 著者: Andreas Naschberger / Rozbeh Baradaran / Bernhard Rupp / Marta Carroni / 要旨: The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to ...The autosomal dominant monogenetic disease neurofibromatosis type 1 (NF1) affects approximately one in 3,000 individuals and is caused by mutations in the NF1 tumour suppressor gene, leading to dysfunction in the protein neurofibromin (Nf1). As a GTPase-activating protein, a key function of Nf1 is repression of the Ras oncogene signalling cascade. We determined the human Nf1 dimer structure at an overall resolution of 3.3 Å. The cryo-electron microscopy structure reveals domain organization and structural details of the Nf1 exon 23a splicing isoform 2 in a closed, self-inhibited, Zn-stabilized state and an open state. In the closed conformation, HEAT/ARM core domains shield the GTPase-activating protein-related domain (GRD) so that Ras binding is sterically inhibited. In a distinctly different, open conformation of one protomer, a large-scale movement of the GRD occurs, which is necessary to access Ras, whereas Sec14-PH reorients to allow interaction with the cellular membrane. Zn incubation of Nf1 leads to reduced Ras-GAP activity with both protomers in the self-inhibited, closed conformation stabilized by a Zn binding site between the N-HEAT/ARM domain and the GRD-Sec14-PH linker. The transition between closed, self-inhibited states of Nf1 and open states provides guidance for targeted studies deciphering the complex molecular mechanism behind the widespread neurofibromatosis syndrome and Nf1 dysfunction in carcinogenesis. | ||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_13398.map.gz | 67.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-13398-v30.xml emd-13398.xml | 12.5 KB 12.5 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_13398_fsc.xml | 9.6 KB | 表示 | FSCデータファイル |
画像 | emd_13398.png | 66.1 KB | ||
マスクデータ | emd_13398_msk_1.map | 75.1 MB | マスクマップ | |
その他 | emd_13398_half_map_1.map.gz emd_13398_half_map_2.map.gz | 58.7 MB 58.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-13398 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-13398 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_13398.map.gz / 形式: CCP4 / 大きさ: 75.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.275 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | emd_13398_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_13398_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_13398_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Homo-dimer of human Neurofibromin Isoform 2
全体 | 名称: Homo-dimer of human Neurofibromin Isoform 2 |
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要素 |
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-超分子 #1: Homo-dimer of human Neurofibromin Isoform 2
超分子 | 名称: Homo-dimer of human Neurofibromin Isoform 2 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
分子量 | 実験値: 640 KDa |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 1.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |