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基本情報
登録情報 | データベース: EMDB / ID: EMD-12367 | ||||||||||||
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タイトル | Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posaconazole-bound, inward-open conformation) | ||||||||||||
![]() | Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posaconazole-bound, inward-open conformation) | ||||||||||||
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機能・相同性 | ![]() response to fenofibrate / Defective ABCB4 causes PFIC3, ICP3 and GBD1 / positive regulation of phospholipid transport / positive regulation of cholesterol transport / positive regulation of phospholipid translocation / bile acid secretion / phospholipid transporter activity / cellular response to bile acid / phosphatidylcholine floppase activity / intercellular canaliculus ...response to fenofibrate / Defective ABCB4 causes PFIC3, ICP3 and GBD1 / positive regulation of phospholipid transport / positive regulation of cholesterol transport / positive regulation of phospholipid translocation / bile acid secretion / phospholipid transporter activity / cellular response to bile acid / phosphatidylcholine floppase activity / intercellular canaliculus / lipid homeostasis / P-type phospholipid transporter / phospholipid translocation / clathrin-coated vesicle / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / lipid metabolic process / PPARA activates gene expression / ABC-family proteins mediated transport / transmembrane transport / apical plasma membrane / membrane raft / focal adhesion / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / membrane / plasma membrane / cytoplasm / cytosol 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: 3.8 Å | ||||||||||||
![]() | Nosol K / Locher KP | ||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Structures of ABCB4 provide insight into phosphatidylcholine translocation. 著者: Kamil Nosol / Rose Bang-Sørensen / Rossitza N Irobalieva / Satchal K Erramilli / Bruno Stieger / Anthony A Kossiakoff / Kaspar P Locher / ![]() ![]() 要旨: ABCB4 is expressed in hepatocytes and translocates phosphatidylcholine into bile canaliculi. The mechanism of specific lipid recruitment from the canalicular membrane, which is essential to mitigate ...ABCB4 is expressed in hepatocytes and translocates phosphatidylcholine into bile canaliculi. The mechanism of specific lipid recruitment from the canalicular membrane, which is essential to mitigate the cytotoxicity of bile salts, is poorly understood. We present cryogenic electron microscopy structures of human ABCB4 in three distinct functional conformations. An apo-inward structure reveals how phospholipid can be recruited from the inner leaflet of the membrane without flipping its orientation. An occluded structure reveals a single phospholipid molecule in a central cavity. Its choline moiety is stabilized by cation-π interactions with an essential tryptophan residue, rationalizing the specificity of ABCB4 for phosphatidylcholine. In an inhibitor-bound structure, a posaconazole molecule blocks phospholipids from reaching the central cavity. Using a proteoliposome-based translocation assay with fluorescently labeled phosphatidylcholine analogs, we recapitulated the substrate specificity of ABCB4 in vitro and confirmed the role of the key tryptophan residue. Our results provide a structural basis for understanding an essential translocation step in the generation of bile and its sensitivity to azole drugs. | ||||||||||||
履歴 |
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 182 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.8 KB 16.8 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 13.8 KB | 表示 | ![]() |
画像 | ![]() | 101.7 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 289.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 288.8 KB | 表示 | |
XML形式データ | ![]() | 14 KB | 表示 | |
CIF形式データ | ![]() | 18.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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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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注釈 | Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posaconazole-bound, inward-open conformation) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.66 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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試料の構成要素
+全体 : Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posac...
+超分子 #1: Nanodisc reconstituted human ABCB4 in complex with 4B1-Fab (posac...
+超分子 #2: phosphatidylcholine translocator ABCB4
+超分子 #3: 4B1 Fab-fragment: light chain
+超分子 #4: 4B1 Fab-fragment: heavy chain
+分子 #1: Phosphatidylcholine translocator ABCB4
+分子 #2: 4B1 Fab-fragment light chain
+分子 #3: 4B1 Fab-fragment heavy chain
+分子 #4: CHOLESTEROL
+分子 #5: POSACONAZOLE
+分子 #6: 1,2-DILINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
-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 | 0.48 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 80.4 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
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 |