+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6q81 | ||||||
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タイトル | Structure of P-glycoprotein(ABCB1) in the post-hydrolytic state | ||||||
要素 | P-glycoprotein (ABCB1) | ||||||
キーワード | MEMBRANE PROTEIN / P-glycoprotein / ABCB1 / ATP-binding cassette / transporter / protein structure | ||||||
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 / cellular response to external biotic stimulus ...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 / cellular response to external biotic stimulus / regulation of intestinal absorption / negative regulation of sensory perception of pain / response to antineoplastic agent / positive regulation of establishment of Sertoli cell barrier / Prednisone ADME / response to alcohol / terpenoid transport / ceramide floppase activity / response to glycoside / floppase activity / ceramide translocation / establishment of blood-retinal barrier / protein localization to bicellular tight junction / cellular response to L-glutamate / ABC-family proteins mediated transport / response to thyroxine / establishment of blood-brain barrier / phosphatidylethanolamine flippase activity / xenobiotic transport across blood-brain barrier / phosphatidylcholine floppase activity / xenobiotic detoxification by transmembrane export across the plasma membrane / intercellular canaliculus / export across plasma membrane / ABC-type xenobiotic transporter / response to vitamin D / P-type phospholipid transporter / ABC-type xenobiotic transporter activity / response to vitamin A / response to glucagon / intestinal absorption / 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 / transmembrane transporter activity / ATPase-coupled transmembrane transporter activity / cellular response to dexamethasone stimulus / response to cadmium ion / cellular response to estradiol stimulus / lactation / placenta development / response to progesterone / female pregnancy / brush border membrane / circadian rhythm / cellular response to tumor necrosis factor / cellular response to lipopolysaccharide / response to hypoxia / apical plasma membrane / response to xenobiotic stimulus / 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: 7.9 Å | ||||||
データ登録者 | Ford, R.C. / Thonghin, N. / Collins, R.F. / Barbieri, A. / Shafi, T. / Siebert, A. | ||||||
引用 | ジャーナル: BMC Struct Biol / 年: 2018 タイトル: Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 Å resolution. 著者: Nopnithi Thonghin / Richard F Collins / Alessandro Barbieri / Talha Shafi / Alistair Siebert / Robert C Ford / 要旨: BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. ...BACKGROUND: P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein. RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP ...RESULTS: In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being located between the NBDs and close to the Signature regions involved in cooperative NBD dimerization. This, and the gap-filling detergent suggest steric impediment to NBD dimerization in the post-hydrolytic state. Two central regions of density lie in two predicted drug-binding sites, implying that the protein may adventitiously bind hydrophobic substances even in the post-hydrolytic state. The previously unresolved N-terminal extension was observed, and the data suggests these 30 residues interact with the headgroup region of the lipid bilayer. CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked ...CONCLUSION: The structural data imply that (i) a low basal ATPase activity is ensured by steric blockers of NBD dimerization and (ii) allocrite access to the central cavity may be structurally linked to NBD dimerization, giving insights into the mechanism of drug-stimulation of P-glycoprotein activity. | ||||||
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 | 6q81.cif.gz | 214.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6q81.ent.gz | 161 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6q81.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 | 6q81_validation.pdf.gz | 892.9 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6q81_full_validation.pdf.gz | 929.2 KB | 表示 | |
XML形式データ | 6q81_validation.xml.gz | 43.6 KB | 表示 | |
CIF形式データ | 6q81_validation.cif.gz | 65 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/q8/6q81 ftp://data.pdbj.org/pub/pdb/validation_reports/q8/6q81 | 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: 140806.766 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 発現宿主: Saccharomyces cerevisiae (パン酵母) / 参照: UniProt: P21447 |
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#2: 化合物 |
-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: P-glycoprotein trapped in the post-hydrolytic state. タイプ: ORGANELLE OR CELLULAR COMPONENT / 詳細: ATP and Vanadate added / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 値: 142 kDa/nm / 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: Saccharomyces cerevisiae (パン酵母) |
緩衝液 | pH: 8 |
試料 | 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: 70 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING ONLY | ||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||
3次元再構成 | 手法: SINGLE PARTICLE / 解像度: 7.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 135357 / 対称性のタイプ: POINT |