+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7otg | ||||||
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タイトル | Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor | ||||||
要素 | Multidrug resistance protein 1A | ||||||
キーワード | MEMBRANE PROTEIN / ABCB1 / ABC Transporters / Membrane Proteins / Ivacaftor / MDR1 / Multidrug resistance / cryo-em | ||||||
機能・相同性 | 機能・相同性情報 hormone transport / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / response to quercetin / negative regulation of sensory perception of pain ...hormone transport / cellular response to borneol / response to codeine / response to cyclosporin A / Atorvastatin ADME / cellular response to mycotoxin / daunorubicin transport / positive regulation of response to drug / response to quercetin / negative regulation of sensory perception of pain / regulation of intestinal absorption / cellular response to external biotic stimulus / response to antineoplastic agent / positive regulation of establishment of Sertoli cell barrier / Prednisone ADME / terpenoid transport / ceramide floppase activity / response to glycoside / ceramide translocation / floppase activity / establishment of blood-retinal barrier / protein localization to bicellular tight junction / response to alcohol / ABC-family proteins mediated transport / phosphatidylethanolamine flippase activity / response to thyroxine / establishment of blood-brain barrier / phosphatidylcholine floppase activity / xenobiotic transport across blood-brain barrier / export across plasma membrane / ABC-type xenobiotic transporter / xenobiotic detoxification by transmembrane export across the plasma membrane / cellular response to L-glutamate / intercellular canaliculus / P-type phospholipid transporter / response to vitamin D / ABC-type xenobiotic transporter activity / response to vitamin A / intestinal absorption / response to glucagon / phospholipid translocation / cellular response to antibiotic / cellular hyperosmotic salinity response / maintenance of blood-brain barrier / cellular response to alkaloid / efflux transmembrane transporter activity / xenobiotic transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / transmembrane transporter activity / response to cadmium ion / lactation / cellular response to dexamethasone stimulus / cellular response to estradiol stimulus / response to progesterone / female pregnancy / brush border membrane / placenta development / circadian rhythm / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / response to xenobiotic stimulus / apical plasma membrane / ATP hydrolysis activity / ATP binding / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||
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: 5.4 Å | ||||||
データ登録者 | Ford, R.C. / Barbieri, A. / Thonghin, N. / Shafi, T. / Prince, S.M. / Collins, R.F. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Membranes (Basel) / 年: 2021 タイトル: Structure of ABCB1/P-Glycoprotein in the Presence of the CFTR Potentiator Ivacaftor. 著者: Alessandro Barbieri / Nopnithi Thonghin / Talha Shafi / Stephen M Prince / Richard F Collins / Robert C Ford / 要旨: ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of ...ABCB1/P-glycoprotein is an ATP binding cassette transporter that is involved in the clearance of xenobiotics, and it affects the disposition of many drugs in the body. Conformational flexibility of the protein within the membrane is an intrinsic part of its mechanism of action, but this has made structural studies challenging. Here, we have studied different conformations of P-glycoprotein simultaneously in the presence of ivacaftor, a known competitive inhibitor. In order to conduct this, we used high contrast cryo-electron microscopy imaging with a Volta phase plate. We associate the presence of ivacaftor with the appearance of an additional density in one of the conformational states detected. The additional density is in the central aqueous cavity and is associated with a wider separation of the two halves of the transporter in the inward-facing state. Conformational changes to the nucleotide-binding domains are also observed and may help to explain the stimulation of ATPase activity that occurs when transported substrate is bound in many ATP binding cassette transporters. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7otg.cif.gz | 212 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7otg.ent.gz | 159.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7otg.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 | 7otg_validation.pdf.gz | 959.4 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7otg_full_validation.pdf.gz | 967.9 KB | 表示 | |
XML形式データ | 7otg_validation.xml.gz | 35.1 KB | 表示 | |
CIF形式データ | 7otg_validation.cif.gz | 53.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ot/7otg ftp://data.pdbj.org/pub/pdb/validation_reports/ot/7otg | 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: 141877.875 Da / 分子数: 1 / Mutation: 0 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Abcb1a, Abcb4, Mdr1a, Mdr3, Pgy-3, Pgy3 / 発現宿主: Komagataella pastoris (菌類) / 参照: UniProt: P21447, xenobiotic-transporting ATPase |
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#2: 化合物 | ChemComp-VX7 / |
研究の焦点であるリガンドがあるか | N |
-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: Structure of ABCB1/P-glycoprotein in the presence of the CFTR potentiator ivacaftor タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
由来(組換発現) | 生物種: Komagataella pastoris (菌類) |
緩衝液 | pH: 8 |
試料 | 濃度: 1.1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-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 |
撮影 | 電子線照射量: 64 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
電子光学装置 | 位相板: VOLTA PHASE PLATE / 球面収差補正装置: 2.7 |
-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: 317000 | ||||||||||||
3次元再構成 | 解像度: 5.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 104000 / クラス平均像の数: 1 / 対称性のタイプ: POINT |