[日本語] English

- EMDB-48276: Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L) -
+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L) | |||||||||
![]() | Composite map, produced through VOP maximum command | |||||||||
![]() |
| |||||||||
![]() | Complex / GTPase / GTP-binding / Autophagy / Kinase / Lipid Kinase / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() extrinsic component of omegasome membrane / phosphatidylinositol 3-kinase inhibitor activity / regulation of triglyceride metabolic process / positive regulation of glycoprotein metabolic process / extrinsic component of phagophore assembly site membrane / nucleus-vacuole junction / cellular response to aluminum ion / positive regulation of protein lipidation / postsynaptic endosome / growth hormone secretion ...extrinsic component of omegasome membrane / phosphatidylinositol 3-kinase inhibitor activity / regulation of triglyceride metabolic process / positive regulation of glycoprotein metabolic process / extrinsic component of phagophore assembly site membrane / nucleus-vacuole junction / cellular response to aluminum ion / positive regulation of protein lipidation / postsynaptic endosome / growth hormone secretion / Toll Like Receptor 9 (TLR9) Cascade / Synthesis of PIPs at the late endosome membrane / positive regulation of stress granule assembly / phosphatidylinositol 3-kinase complex, class III / cellular response to oxygen-glucose deprivation / Synthesis of PIPs at the early endosome membrane / phosphatidylinositol 3-kinase complex, class III, type II / phosphatidylinositol 3-kinase complex, class III, type I / response to mitochondrial depolarisation / host-mediated activation of viral genome replication / presynaptic endosome / positive regulation of attachment of mitotic spindle microtubules to kinetochore / mitochondria-associated endoplasmic reticulum membrane contact site / COPII-coated vesicle cargo loading / negative regulation of lysosome organization / engulfment of apoptotic cell / Synthesis of PIPs at the Golgi membrane / phosphatidylinositol kinase activity / regulation of protein complex stability / positive regulation of autophagosome assembly / early endosome to late endosome transport / response to L-leucine / cytoplasmic side of mitochondrial outer membrane / negative regulation of autophagosome assembly / protein localization to phagophore assembly site / phosphatidylinositol 3-kinase regulator activity / receptor catabolic process / phagophore assembly site membrane / protein targeting to vacuole / RAB geranylgeranylation / protein targeting to lysosome / SMAD protein signal transduction / late endosome to vacuole transport / endosome organization / melanosome transport / pexophagy / RAB GEFs exchange GTP for GDP on RABs / Golgi Cisternae Pericentriolar Stack Reorganization / vesicle transport along microtubule / phagophore assembly site / Translation of Replicase and Assembly of the Replication Transcription Complex / phosphatidylinositol-3-phosphate biosynthetic process / cellular response to nitrogen starvation / COPII-mediated vesicle transport / negative regulation of programmed cell death / phosphatidylinositol 3-kinase / COPI-dependent Golgi-to-ER retrograde traffic / 1-phosphatidylinositol-3-kinase activity / lysosome organization / response to vitamin E / post-transcriptional regulation of gene expression / response to iron(II) ion / mitotic metaphase chromosome alignment / cytoplasmic pattern recognition receptor signaling pathway / endosome to lysosome transport / transport vesicle membrane / virion assembly / positive regulation of cardiac muscle hypertrophy / phosphatidylinositol-mediated signaling / Macroautophagy / autophagosome membrane docking / RSV-host interactions / p38MAPK cascade / Golgi organization / phosphatidylinositol phosphate biosynthetic process / negative regulation of protein phosphorylation / autolysosome / autophagosome membrane / PI3K Cascade / axoneme / synaptic vesicle endocytosis / autophagosome assembly / RHO GTPases Activate NADPH Oxidases / autophagosome maturation / amyloid-beta metabolic process / regulation of macroautophagy / endoplasmic reticulum to Golgi vesicle-mediated transport / neuron development / cellular defense response / cellular response to glucose starvation / mitophagy / phosphatidylinositol 3-kinase binding / intercellular bridge / positive regulation of intrinsic apoptotic signaling pathway / COPI-mediated anterograde transport / vesicle-mediated transport / phagocytic vesicle / JNK cascade / protein-membrane adaptor activity / positive regulation of autophagy 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: 2.73 Å | |||||||||
![]() | Cook ASI / Hurley JH / Chen M | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: Structural pathway for PI3-kinase regulation by VPS15 in autophagy. 著者: Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou / ...著者: Annan S I Cook / Minghao Chen / Thanh N Nguyen / Ainara Claveras Cabezudo / Grace Khuu / Shanlin Rao / Samantha N Garcia / Mingxuan Yang / Anthony T Iavarone / Xuefeng Ren / Michael Lazarou / Gerhard Hummer / James H Hurley / ![]() ![]() ![]() 要旨: The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway ...The class III phosphatidylinositol-3 kinase complexes I and II (PI3KC3-C1 and PI3KC3-C2) have vital roles in macroautophagy and endosomal maturation, respectively. We elucidated a structural pathway of enzyme activation through cryo-electron microscopy analysis of PI3KC3-C1. The inactive conformation of the VPS15 pseudokinase stabilizes the inactive conformation, sequestering its -myristate in the N-lobe of the pseudokinase. Upon activation, the myristate is liberated such that the VPS34 lipid kinase catalyzes phosphatidylinositol-3 phosphate production on membranes. The VPS15 pseudokinase domain binds tightly to guanosine triphosphate and stabilizes a web of interactions to autoinhibit the cytosolic complex and promote activation upon membrane binding. These findings show in atomistic detail how the VPS34 lipid kinase is activated in the context of a complete PI3K complex. | |||||||||
履歴 |
|
-
構造の表示
添付画像 |
---|
-
ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 226.6 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 28.1 KB 28.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 39.6 KB | ||
Filedesc metadata | ![]() | 9.4 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 493 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 492.6 KB | 表示 | |
XML形式データ | ![]() | 7.1 KB | 表示 | |
CIF形式データ | ![]() | 8.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 9mhfMC ![]() 9mhgC ![]() 9mhhC C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | Composite map, produced through VOP maximum command | ||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.048 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-
試料の構成要素
+全体 : Phosphatidylinositol-3 kinase class III complex I bound to RAB1A
+超分子 #1: Phosphatidylinositol-3 kinase class III complex I bound to RAB1A
+分子 #1: Phosphoinositide 3-kinase regulatory subunit 4
+分子 #2: Phosphatidylinositol 3-kinase catalytic subunit type 3
+分子 #3: Beclin 1-associated autophagy-related key regulator
+分子 #4: Beclin-1
+分子 #5: Ras-related protein Rab-1A
+分子 #6: GUANOSINE-5'-TRIPHOSPHATE
+分子 #7: MAGNESIUM ION
+分子 #8: MYRISTIC ACID
+分子 #9: water
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
![]() | 単粒子再構成法 |
試料の集合状態 | particle |
-
試料調製
濃度 | 0.2 mg/mL | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
緩衝液 | pH: 7.4 構成要素:
| |||||||||||||||
グリッド | モデル: Quantifoil Active R2/1 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. / 詳細: 25 mA | |||||||||||||||
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 |
-
電子顕微鏡法
顕微鏡 | TFS KRIOS |
---|---|
特殊光学系 | エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 19300 / 平均電子線量: 50.0 e/Å2 |
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): 2.0 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 |
+
画像解析
-原子モデル構築 1
初期モデル | Chain - Source name: AlphaFold / Chain - Initial model type: in silico model |
---|---|
ソフトウェア | 名称: ISOLDE (ver. 1.7) |
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
得られたモデル | ![]() PDB-9mhf: |