+データを開く
-基本情報
登録情報 | データベース: SASBDB / ID: SASDD76 |
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試料 | Phox Homologue (PX) - C2 domains of human phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3KC2α) in complex with inositol-hexaphosphate (IP6)
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機能・相同性 | 機能・相同性情報 vascular associated smooth muscle contraction / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol-4-phosphate 3-kinase / clathrin coat assembly / membrane organization / phosphatidylinositol biosynthetic process / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity ...vascular associated smooth muscle contraction / Synthesis of PIPs at the late endosome membrane / Synthesis of PIPs at the early endosome membrane / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol-4-phosphate 3-kinase / clathrin coat assembly / membrane organization / phosphatidylinositol biosynthetic process / phosphatidylinositol 3-kinase complex / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / PI3キナーゼ / クラスリン / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / clathrin binding / positive regulation of cell migration involved in sprouting angiogenesis / Golgi Associated Vesicle Biogenesis / エキソサイトーシス / Synthesis of PIPs at the plasma membrane / platelet-derived growth factor receptor signaling pathway / positive regulation of autophagy / phosphatidylinositol binding / phosphatidylinositol 3-kinase/protein kinase B signal transduction / epidermal growth factor receptor signaling pathway / ゴルジ体 / エンドサイトーシス / insulin receptor signaling pathway / Clathrin-mediated endocytosis / vesicle / リン酸化 / intracellular membrane-bounded organelle / extracellular exosome / 核質 / ATP binding / 生体膜 / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 |
生物種 | Homo sapiens (ヒト) |
引用 | ジャーナル: Structure / 年: 2018 タイトル: Molecular Basis for Membrane Recruitment by the PX and C2 Domains of Class II Phosphoinositide 3-Kinase-C2α. 著者: Kai-En Chen / Vikas A Tillu / Mintu Chandra / Brett M Collins / 要旨: Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated ...Phosphorylation of phosphoinositides by the class II phosphatidylinositol 3-kinase (PI3K) PI3K-C2α is essential for many processes, including neuroexocytosis and formation of clathrin-coated vesicles. A defining feature of the class II PI3Ks is a C-terminal module composed of phox-homology (PX) and C2 membrane interacting domains; however, the mechanisms that control their specific cellular localization remain poorly understood. Here we report the crystal structure of the C2 domain of PI3K-C2α in complex with the phosphoinositide head-group mimic inositol hexaphosphate, revealing two distinct pockets for membrane binding. The C2 domain preferentially binds to phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate, and low-resolution structures of the combined PX-C2 module by small-angle X-ray scattering reveal a compact conformation in which cooperative lipid binding by each domain binding can occur. Finally, we demonstrate an unexpected role for calcium in perturbing the membrane interactions of the PX-C2 module, which we speculate may be important for regulating the activity of PI3K-C2α. |
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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
-Data source
SASBDBのページ | SASDD76 |
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-関連構造データ
-外部リンク
「今月の分子」の関連する項目 |
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-モデル
モデル #1923 | タイプ: dummy / ソフトウェア: (5.0) / ダミー原子の半径: 2.25 A / カイ2乗値: 0.204 Omokage検索でこの集合体の類似形状データを探す (詳細) |
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モデル #1958 | タイプ: dummy / ダミー原子の半径: 2.40 A / カイ2乗値: 0.204 Omokage検索でこの集合体の類似形状データを探す (詳細) |
モデル #1924 | タイプ: mix / ソフトウェア: (5) / ダミー原子の半径: 2.00 A コメント: PDB code of PX domain (6BUB) and C2 domain - IP6 complex (6BU0) カイ2乗値: 0.17 Omokage検索でこの集合体の類似形状データを探す (詳細) |
-試料
試料 | 名称: Phox Homologue (PX) - C2 domains of human phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3KC2α) in complex with inositol-hexaphosphate (IP6) 試料濃度: 10.5 mg/ml |
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バッファ | 名称: 25 mM Tris 200 mM NaCl 5% Glycerol 0.5 mM TCEP 4 mM InsP6 pH: 8.5 コメント: 4 mM InsP6 (10 molar excess) was added to the protein sample a day before the data collection |
要素 #1041 | 名称: PI3KC2α / タイプ: protein 記述: Phox Homology (PX) - C2 domains of human Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha 分子量: 32.663 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: O00443 配列: SNADEPILSF SPKTYSFRQD GRIKEVSVFT YHKKYNPDKH YIYVVRILRE GQIEPSFVFR TFDEFQELHN KLSIIFPLWK LPGFPNRMVL GRTHAKDVAA KRKIELNSYL QSLMNASTDV AECDLVCTFF HPLLRDEKAE GIARSADAGS FSPTPGQIGG AVKLSISYRN ...配列: SNADEPILSF SPKTYSFRQD GRIKEVSVFT YHKKYNPDKH YIYVVRILRE GQIEPSFVFR TFDEFQELHN KLSIIFPLWK LPGFPNRMVL GRTHAKDVAA KRKIELNSYL QSLMNASTDV AECDLVCTFF HPLLRDEKAE GIARSADAGS FSPTPGQIGG AVKLSISYRN GTLFIMVMHI KDLVTEDGAD PNPYVKTYLL PDNHKTSKRK TKISRKTRNP TFNEMLVYSG YSKETLRQRE LQLSVLSAES LRENFFLGGV TLPLKDFNLS KETVKWYQLT AATYL |
-実験情報
ビーム | 設備名称: Australian Synchrotron SAXS/WAXS / 地域: Melbourne / 国: Australia / 形状: Point / 線源: X-ray synchrotronシンクロトロン / 波長: 0.10332 Å | ||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 1M / タイプ: Dectris / Pixsize x: 172 mm | ||||||||||||||||||||||||||||||
スキャン | タイトル: Phox Homology (PX) - C2 domains of human phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha (PI3KC2α) n complex with inositol-6-phosphate 測定日: 2017年10月20日 / セル温度: 10 °C / 照射時間: 1 sec. / フレーム数: 15 / 単位: 1/A /
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距離分布関数 P(R) | ソフトウェア P(R): GNOM 5.0 / ポイント数: 179 /
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結果 | カーブのタイプ: sec コメント: SEC-SAXS details: Column type: S200 5/150 GL column; Flow rate: 0.45 ml/min; Sample temperature, 10°C; Sample injection concentration: 10.5 mg/ml. The ab initio models represent the ...コメント: SEC-SAXS details: Column type: S200 5/150 GL column; Flow rate: 0.45 ml/min; Sample temperature, 10°C; Sample injection concentration: 10.5 mg/ml. The ab initio models represent the spatially aligned and volume occupancy corrected (averaged) representation of the protein obtained from 20 individual reconstructions (top, DAMFILT model: NSD = 0.66 +/- 0.02; resolution estimate = 3.3 nm) and the best-fit individual DAMMIN reconstruction (bottom) displayed with the corresponding individual model fit to the SAXS data.
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