+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9f45 | |||||||||
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タイトル | cryo-EM structure of human LST2 bound to human mTOR complex 1 | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN / MTOR / MTORC1 / LST2 / ZFYVE28 / EGFR / TOS | |||||||||
機能・相同性 | 機能・相同性情報 negative regulation of epidermal growth factor-activated receptor activity / RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / TORC2 complex / cellular response to leucine starvation ...negative regulation of epidermal growth factor-activated receptor activity / RNA polymerase III type 2 promoter sequence-specific DNA binding / RNA polymerase III type 1 promoter sequence-specific DNA binding / positive regulation of cytoplasmic translational initiation / regulation of locomotor rhythm / T-helper 1 cell lineage commitment / positive regulation of pentose-phosphate shunt / positive regulation of wound healing, spreading of epidermal cells / TORC2 complex / cellular response to leucine starvation / TFIIIC-class transcription factor complex binding / regulation of membrane permeability / negative regulation of lysosome organization / heart valve morphogenesis / nucleus localization / RNA polymerase III type 3 promoter sequence-specific DNA binding / TORC1 complex / positive regulation of transcription of nucleolar large rRNA by RNA polymerase I / calcineurin-NFAT signaling cascade / voluntary musculoskeletal movement / TORC1 signaling / regulation of osteoclast differentiation / positive regulation of odontoblast differentiation / positive regulation of keratinocyte migration / cellular response to L-leucine / Amino acids regulate mTORC1 / MTOR signalling / cellular response to nutrient / regulation of autophagosome assembly / cellular response to methionine / Energy dependent regulation of mTOR by LKB1-AMPK / energy reserve metabolic process / negative regulation of cell size / ruffle organization / phosphatidylinositol-3-phosphate binding / positive regulation of osteoclast differentiation / cellular response to osmotic stress / protein serine/threonine kinase inhibitor activity / enzyme-substrate adaptor activity / negative regulation of protein localization to nucleus / anoikis / cardiac muscle cell development / positive regulation of transcription by RNA polymerase III / negative regulation of calcineurin-NFAT signaling cascade / regulation of myelination / positive regulation of actin filament polymerization / regulation of cell size / negative regulation of macroautophagy / positive regulation of oligodendrocyte differentiation / lysosome organization / Macroautophagy / positive regulation of myotube differentiation / protein kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / behavioral response to pain / oligodendrocyte differentiation / Constitutive Signaling by AKT1 E17K in Cancer / mTORC1-mediated signalling / germ cell development / : / CD28 dependent PI3K/Akt signaling / social behavior / HSF1-dependent transactivation / neuronal action potential / positive regulation of TOR signaling / response to amino acid / TOR signaling / endomembrane system / 'de novo' pyrimidine nucleobase biosynthetic process / regulation of macroautophagy / positive regulation of translational initiation / positive regulation of G1/S transition of mitotic cell cycle / cellular response to nutrient levels / positive regulation of lamellipodium assembly / phagocytic vesicle / heart morphogenesis / positive regulation of lipid biosynthetic process / positive regulation of epithelial to mesenchymal transition / phosphorylation / cardiac muscle contraction / regulation of cellular response to heat / positive regulation of stress fiber assembly / cytoskeleton organization / 14-3-3 protein binding / positive regulation of endothelial cell proliferation / T cell costimulation / cellular response to amino acid starvation / cellular response to starvation / post-embryonic development / positive regulation of glycolytic process / negative regulation of autophagy / protein serine/threonine kinase activator activity / response to nutrient / response to nutrient levels / VEGFR2 mediated vascular permeability / regulation of signal transduction by p53 class mediator / positive regulation of peptidyl-threonine phosphorylation / positive regulation of translation / Regulation of PTEN gene transcription / regulation of autophagy 類似検索 - 分子機能 | |||||||||
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: 3.74 Å | |||||||||
データ登録者 | Craigie, L.M. / Maier, T. | |||||||||
資金援助 | スイス, European Union, 2件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2024 タイトル: mTORC1 phosphorylates and stabilizes LST2 to negatively regulate EGFR. 著者: Stefania Battaglioni / Louise-Marie Craigie / Sofia Filippini / Timm Maier / Michael N Hall / 要旨: TORC1 (target of rapamycin complex 1) is a highly conserved protein kinase that plays a central role in regulating cell growth. Given the role of mammalian TORC1 (mTORC1) in metabolism and disease, ...TORC1 (target of rapamycin complex 1) is a highly conserved protein kinase that plays a central role in regulating cell growth. Given the role of mammalian TORC1 (mTORC1) in metabolism and disease, understanding mTORC1 downstream signaling and feedback loops is important. mTORC1 recognizes some of its substrates via a five amino acid binding sequence called the TOR signaling (TOS) motif. mTORC1 binding to a TOS motif facilitates phosphorylation of a distinct, distal site. Here, we show that LST2, also known as ZFYVE28, contains a TOS motif (amino acids 401 to 405) and is directly phosphorylated by mTORC1 at serine 670 (S670). mTORC1-mediated S670 phosphorylation promotes LST2 monoubiquitination on lysine 87 (K87). Monoubiquitinated LST2 is stable and displays a broad reticular distribution. When mTORC1 is inactive, unphosphorylated LST2 is degraded by the proteasome. The absence of LST2 enhances EGFR (epidermal growth factor receptor) signaling. We propose that mTORC1 negatively feeds back on its upstream receptor EGFR via LST2. | |||||||||
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 | 9f45.cif.gz | 1.3 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9f45.ent.gz | 1 MB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9f45.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
文書・要旨 | 9f45_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9f45_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 9f45_validation.xml.gz | 176.6 KB | 表示 | |
CIF形式データ | 9f45_validation.cif.gz | 271.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f4/9f45 ftp://data.pdbj.org/pub/pdb/validation_reports/f4/9f45 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 289257.969 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P42345, non-specific serine/threonine protein kinase #2: タンパク質 | 分子量: 35910.090 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: MLST8, GBL, LST8 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9BVC4 #3: タンパク質 | 分子量: 152764.656 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: RPTOR, KIAA1303, RAPTOR 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q8N122 #4: タンパク質 | 分子量: 96604.477 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ZFYVE28, KIAA1643, LST2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9HCC9 #5: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: mTORC1 in complex with LST2 / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 8 |
試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R2/1 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 95 % / 凍結前の試料温度: 281 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 43 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 1 / 実像数: 4719 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1057805 | |||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | |||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.74 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 272762 / 対称性のタイプ: POINT | |||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 7PEB Accession code: 7PEB / Source name: PDB / タイプ: experimental model | |||||||||||||||||||||||||||
拘束条件 |
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