+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6cu6 | ||||||
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タイトル | Crystal structure of GMPPNP-bound G12R mutant of human KRAS4b | ||||||
要素 | GTPase KRas | ||||||
キーワード | ONCOPROTEIN (がん遺伝子) / KRAS (KRAS) / RAS / G12R / G12 / KRAS4b / K-RAS (KRAS) | ||||||
機能・相同性 | 機能・相同性情報 forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants ...forebrain astrocyte development / regulation of synaptic transmission, GABAergic / negative regulation of epithelial cell differentiation / epithelial tube branching involved in lung morphogenesis / type I pneumocyte differentiation / Rac protein signal transduction / skeletal muscle cell differentiation / positive regulation of Rac protein signal transduction / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / RAS signaling downstream of NF1 loss-of-function variants / RUNX3 regulates p14-ARF / SOS-mediated signalling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / SHC1 events in ERBB4 signaling / Signalling to RAS / glial cell proliferation / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Estrogen-stimulated signaling through PRKCZ / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / protein-membrane adaptor activity / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / homeostasis of number of cells within a tissue / positive regulation of glial cell proliferation / FRS-mediated FGFR3 signaling / Signaling by CSF3 (G-CSF) / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / p38MAPK events / FRS-mediated FGFR1 signaling / Tie2 Signaling / Signaling by FGFR2 in disease / GRB2 events in EGFR signaling / striated muscle cell differentiation / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / Ras activation upon Ca2+ influx through NMDA receptor / FLT3 Signaling / Signaling by FGFR1 in disease / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / Insulin receptor signalling cascade / Constitutive Signaling by Overexpressed ERBB2 / 低分子量GTPアーゼ / G protein activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / VEGFR2 mediated cell proliferation / FCERI mediated MAPK activation / regulation of long-term neuronal synaptic plasticity / Signaling by ERBB2 TMD/JMD mutants / RAF activation / Signaling by high-kinase activity BRAF mutants / Constitutive Signaling by EGFRvIII / visual learning / MAP2K and MAPK activation / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Signaling by SCF-KIT / cytoplasmic side of plasma membrane / Regulation of RAS by GAPs / Negative regulation of MAPK pathway / RAS processing / GDP binding / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by CSF1 (M-CSF) in myeloid cells / 分裂促進因子活性化タンパク質キナーゼ / Signaling by BRAF and RAF1 fusions / Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants / DAP12 signaling / Ca2+ pathway / 遺伝子発現 / actin cytoskeleton organization / RAF/MAP kinase cascade / neuron apoptotic process / Ras protein signal transduction / negative regulation of neuron apoptotic process / mitochondrial outer membrane / positive regulation of protein phosphorylation / ゴルジ体 / focal adhesion 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | X線回折 / シンクロトロン / 分子置換 / 解像度: 1.5 Å | ||||||
データ登録者 | Tran, T.H. / Simanshu, D.K. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cancer Discov / 年: 2020 タイトル: Atypical KRASG12RMutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer. 著者: Hobbs, G.A. / Baker, N.M. / Miermont, A.M. / Thurman, R.D. / Pierobon, M. / Tran, T.H. / Anderson, A.O. / Waters, A.M. / Diehl, J.N. / Papke, B. / Hodge, R.G. / Klomp, J.E. / Goodwin, C.M. / ...著者: Hobbs, G.A. / Baker, N.M. / Miermont, A.M. / Thurman, R.D. / Pierobon, M. / Tran, T.H. / Anderson, A.O. / Waters, A.M. / Diehl, J.N. / Papke, B. / Hodge, R.G. / Klomp, J.E. / Goodwin, C.M. / DeLiberty, J.M. / Wang, J. / Ng, R.W.S. / Gautam, P. / Bryant, K.L. / Esposito, D. / Campbell, S.L. / Petricoin 3rd, E.F. / Simanshu, D.K. / Aguirre, A.J. / Wolpin, B.M. / Wennerberg, K. / Rudloff, U. / Cox, A.D. / Der, C.J. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6cu6.cif.gz | 120.4 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6cu6.ent.gz | 91.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6cu6.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/cu/6cu6 ftp://data.pdbj.org/pub/pdb/validation_reports/cu/6cu6 | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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3 |
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単位格子 |
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Components on special symmetry positions |
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-要素
#1: タンパク質 | 分子量: 19428.953 Da / 分子数: 3 / 変異: G12R / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: KRAS, KRAS2, RASK2 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P01116 #2: 化合物 | #3: 化合物 | #4: 化合物 | ChemComp-GOL / | #5: 水 | ChemComp-HOH / | |
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-実験情報
-実験
実験 | 手法: X線回折 / 使用した結晶の数: 1 |
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-試料調製
結晶 | マシュー密度: 1.97 Å3/Da / 溶媒含有率: 37.56 % |
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結晶化 | 温度: 293 K / 手法: 蒸気拡散法, シッティングドロップ法 / pH: 7.5 詳細: 2.1 M Sodium Malonate pH 7.5, 40 mM Dimethyloctylphosphine oxide |
-データ収集
回折 | 平均測定温度: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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放射光源 | 由来: シンクロトロン / サイト: APS / ビームライン: 24-ID-E / 波長: 0.97918 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
検出器 | タイプ: DECTRIS EIGER X 16M / 検出器: PIXEL / 日付: 2017年8月3日 詳細: Cryogenically-cooled single crystal Si(220) side bounce monochromator | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
放射 | プロトコル: SINGLE WAVELENGTH / 単色(M)・ラウエ(L): M / 散乱光タイプ: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
放射波長 | 波長: 0.97918 Å / 相対比: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 | 解像度: 1.5→50.58 Å / Num. obs: 70088 / % possible obs: 95.5 % / 冗長度: 2.325 % / Biso Wilson estimate: 26.11 Å2 / CC1/2: 0.997 / Rmerge(I) obs: 0.048 / Rrim(I) all: 0.061 / Χ2: 1.18 / Net I/σ(I): 8.93 / Num. measured all: 317030 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
反射 シェル | Diffraction-ID: 1
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-解析
ソフトウェア |
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精密化 | 構造決定の手法: 分子置換 開始モデル: GMPPNP-bound KRAS4B 解像度: 1.5→50.58 Å / SU ML: 0.21 / 交差検証法: THROUGHOUT / σ(F): 1.37 / 位相誤差: 29.1
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溶媒の処理 | 減衰半径: 0.9 Å / VDWプローブ半径: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso max: 115.27 Å2 / Biso mean: 40.7487 Å2 / Biso min: 18 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化ステップ | サイクル: final / 解像度: 1.5→50.58 Å
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LS精密化 シェル | Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 13
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