+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9f43 | |||||||||
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タイトル | cryo-EM structure of human LST2 bound to human mTOR complex 1, focused on RAPTOR | |||||||||
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 / positive regulation of pentose-phosphate shunt / TORC1 complex / TORC1 signaling / positive regulation of odontoblast differentiation / cellular response to L-leucine / Amino acids regulate mTORC1 / MTOR signalling / Energy dependent regulation of mTOR by LKB1-AMPK / phosphatidylinositol-3-phosphate binding ...negative regulation of epidermal growth factor-activated receptor activity / positive regulation of pentose-phosphate shunt / TORC1 complex / TORC1 signaling / positive regulation of odontoblast differentiation / cellular response to L-leucine / Amino acids regulate mTORC1 / MTOR signalling / Energy dependent regulation of mTOR by LKB1-AMPK / phosphatidylinositol-3-phosphate binding / positive regulation of osteoclast differentiation / cellular response to osmotic stress / protein serine/threonine kinase inhibitor activity / enzyme-substrate adaptor activity / positive regulation of transcription by RNA polymerase III / regulation of cell size / Macroautophagy / protein kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / mTORC1-mediated signalling / social behavior / HSF1-dependent transactivation / positive regulation of TOR signaling / TOR signaling / positive regulation of G1/S transition of mitotic cell cycle / cellular response to nutrient levels / positive regulation of lipid biosynthetic process / 14-3-3 protein binding / positive regulation of endothelial cell proliferation / cellular response to starvation / positive regulation of glycolytic process / negative regulation of autophagy / positive regulation of peptidyl-threonine phosphorylation / Regulation of PTEN gene transcription / regulation of autophagy / regulation of cell growth / cellular response to amino acid stimulus / TP53 Regulates Metabolic Genes / cellular response to glucose stimulus / small GTPase binding / cytoplasmic stress granule / positive regulation of peptidyl-serine phosphorylation / protein-macromolecule adaptor activity / cellular response to hypoxia / early endosome membrane / positive regulation of cell growth / lysosome / response to xenobiotic stimulus / lysosomal membrane / neuronal cell body / DNA damage response / dendrite / protein-containing complex binding / protein kinase binding / nucleoplasm / metal ion binding / cytosol / cytoplasm 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: 3.49 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 | 9f43.cif.gz | 249.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9f43.ent.gz | 179.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 9f43.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 | 9f43_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 9f43_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 9f43_validation.xml.gz | 51.6 KB | 表示 | |
CIF形式データ | 9f43_validation.cif.gz | 74.5 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/f4/9f43 ftp://data.pdbj.org/pub/pdb/validation_reports/f4/9f43 | 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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1 |
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-要素
#1: タンパク質 | 分子量: 152764.656 Da / 分子数: 1 / 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 |
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#2: タンパク質 | 分子量: 96604.477 Da / 分子数: 1 / 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 |
-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: all / 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: 3.49 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 545524 / 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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