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基本情報
登録情報 | データベース: EMDB / ID: EMD-23812 | |||||||||
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タイトル | Structure of the apo phosphoinositide 3-kinase p110 gamma (PIK3CG) p101 (PIK3R5) complex | |||||||||
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機能・相同性 | ![]() : / secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport ...: / secretory granule localization / negative regulation of triglyceride catabolic process / natural killer cell chemotaxis / neutrophil extravasation / phosphatidylinositol-4-phosphate 3-kinase / positive regulation of acute inflammatory response / respiratory burst involved in defense response / negative regulation of cardiac muscle contraction / regulation of calcium ion transmembrane transport / 1-phosphatidylinositol-3-kinase regulator activity / T cell chemotaxis / negative regulation of fibroblast apoptotic process / phosphatidylinositol 3-kinase complex, class IB / sphingosine-1-phosphate receptor signaling pathway / phosphatidylinositol 3-kinase complex, class IA / phosphatidylinositol 3-kinase complex / dendritic cell chemotaxis / 1-phosphatidylinositol-4-phosphate 3-kinase activity / 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity / phosphatidylinositol-4,5-bisphosphate 3-kinase / phosphatidylinositol 3-kinase / phosphatidylinositol-3-phosphate biosynthetic process / 1-phosphatidylinositol-3-kinase activity / mast cell degranulation / Erythropoietin activates Phosphoinositide-3-kinase (PI3K) / hepatocyte apoptotic process / positive regulation of Rac protein signal transduction / Synthesis of PIPs at the plasma membrane / regulation of cell adhesion mediated by integrin / phosphatidylinositol-mediated signaling / phosphatidylinositol phosphate biosynthetic process / centriolar satellite / regulation of angiogenesis / T cell proliferation / cellular response to cAMP / GPVI-mediated activation cascade / T cell activation / neutrophil chemotaxis / ephrin receptor binding / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of endothelial cell migration / phosphorylation / positive regulation of cytokine production / positive regulation of MAP kinase activity / G-protein beta/gamma-subunit complex binding / platelet aggregation / G beta:gamma signalling through PI3Kgamma / endocytosis / kinase activity / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / angiogenesis / adaptive immune response / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / protein kinase activity / inflammatory response / immune response / G protein-coupled receptor signaling pathway / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.36 Å | |||||||||
![]() | Burke JE / Dalwadi U / Rathinaswamy MK / Yip CK | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation. 著者: Manoj K Rathinaswamy / Udit Dalwadi / Kaelin D Fleming / Carson Adams / Jordan T B Stariha / Els Pardon / Minkyung Baek / Oscar Vadas / Frank DiMaio / Jan Steyaert / Scott D Hansen / Calvin K ...著者: Manoj K Rathinaswamy / Udit Dalwadi / Kaelin D Fleming / Carson Adams / Jordan T B Stariha / Els Pardon / Minkyung Baek / Oscar Vadas / Frank DiMaio / Jan Steyaert / Scott D Hansen / Calvin K Yip / John E Burke / ![]() ![]() ![]() ![]() 要旨: The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function ...The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function is the association of the p110γ catalytic subunit to either a p101 or p84 regulatory subunit, which mediates activation by G protein-coupled receptors. Here, we report the cryo-electron microscopy structure of a heterodimeric PI3Kγ complex, p110γ-p101. This structure reveals a unique assembly of catalytic and regulatory subunits that is distinct from other class I PI3K complexes. p101 mediates activation through its Gβγ-binding domain, recruiting the heterodimer to the membrane and allowing for engagement of a secondary Gβγ-binding site in p110γ. Mutations at the p110γ-p101 and p110γ-adaptor binding domain interfaces enhanced Gβγ activation. A nanobody that specifically binds to the p101-Gβγ interface blocks activation, providing a novel tool to study and target p110γ-p101-specific signaling events in vivo. | |||||||||
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 97.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 14.6 KB 14.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.5 KB | 表示 | ![]() |
画像 | ![]() | 97.9 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.079 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
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試料の構成要素
-全体 : Complex of p110 gamma with p101
全体 | 名称: Complex of p110 gamma with p101 |
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要素 |
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-超分子 #1: Complex of p110 gamma with p101
超分子 | 名称: Complex of p110 gamma with p101 / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 詳細: p110 subunit is from homo sapiens, p101 is from Sus scrofa |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() ![]() |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.4 mg/mL | |||||||||||||||
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緩衝液 | pH: 8.5 構成要素:
詳細: Freshly prepared gel filtration buffer, filtered through 0.22um filter and degassed | |||||||||||||||
グリッド | モデル: C-flat-2/2 / 材質: COPPER / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR / 前処理 - 気圧: 0.039 kPa 詳細: Glow discharged using a Pelco EasiGlow. 15mA current. | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: 1.5s blot time, -5 blot force. | |||||||||||||||
詳細 | Specimen was a 1:1 molar ratio of p110g-p101, purified to homogeneity by gel filtration. |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
詳細 | PNCC Krios 4 |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 6153 / 平均電子線量: 50.0 e/Å2 詳細: Movies were collected in super-resolution mode set to collect 3 shots per grid hole over 5 holes by beam-shift before applying a stage shift. |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 81000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |