+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8560 | ||||||||||||
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タイトル | Cryo-EM structure of bovine multidrug resistance protein 1 (MRP1) bound to leukotriene C4 | ||||||||||||
マップデータ | Full map translated into unit cell used for reciprocal space refinement, sharpened with a B-factor of -100 A^2 and a resolution cutoff of 3.34 A | ||||||||||||
試料 |
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キーワード | ABC transporter / multidrug resistance (多剤耐性) / leukotriene C4 / LTC4 / PROTEIN TRANSPORT | ||||||||||||
機能・相同性 | 機能・相同性情報 Heme degradation / Synthesis of Leukotrienes (LT) and Eoxins (EX) / cyclic nucleotide transport / Transport of RCbl within the body / Paracetamol ADME / leukotriene transport / glutathione transmembrane transporter activity / glutathione transmembrane transport / ABC-type glutathione-S-conjugate transporter / ABC-type glutathione S-conjugate transporter activity ...Heme degradation / Synthesis of Leukotrienes (LT) and Eoxins (EX) / cyclic nucleotide transport / Transport of RCbl within the body / Paracetamol ADME / leukotriene transport / glutathione transmembrane transporter activity / glutathione transmembrane transport / ABC-type glutathione-S-conjugate transporter / ABC-type glutathione S-conjugate transporter activity / ABC-family proteins mediated transport / Cytoprotection by HMOX1 / ABC-type xenobiotic transporter / ABC-type xenobiotic transporter activity / xenobiotic transport / lipid transport / xenobiotic transmembrane transporter activity / ABC-type transporter activity / positive regulation of inflammatory response / basolateral plasma membrane / response to xenobiotic stimulus / ATP hydrolysis activity / ATP binding 類似検索 - 分子機能 | ||||||||||||
生物種 | Bos taurus (ウシ) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.34 Å | ||||||||||||
データ登録者 | Johnson ZL / Chen J | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Cell / 年: 2017 タイトル: Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1. 著者: Zachary Lee Johnson / Jue Chen / 要旨: The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several ...The multidrug resistance protein MRP1 is an ATP-binding cassette (ABC) transporter that confers resistance to many anticancer drugs and plays a role in the disposition and efficacy of several opiates, antidepressants, statins, and antibiotics. In addition, MRP1 regulates redox homeostasis, inflammation, and hormone secretion. Using electron cryomicroscopy, we determined the molecular structures of bovine MRP1 in two conformations: an apo form at 3.5 Å without any added substrate and a complex form at 3.3 Å with one of its physiological substrates, leukotriene C. These structures show that by forming a single bipartite binding site, MRP1 can recognize a spectrum of substrates with different chemical structures. We also observed large conformational changes induced by leukotriene C, explaining how substrate binding primes the transporter for ATP hydrolysis. Structural comparison of MRP1 and P-glycoprotein advances our understanding of the common and unique properties of these two important molecules in multidrug resistance to chemotherapy. | ||||||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
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 | emd_8560.map.gz | 199.8 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8560-v30.xml emd-8560.xml | 23.6 KB 23.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8560.png | 148.9 KB | ||
Filedesc metadata | emd-8560.cif.gz | 7.1 KB | ||
その他 | emd_8560_additional.map.gz emd_8560_half_map_1.map.gz emd_8560_half_map_2.map.gz | 196.7 MB 199.5 MB 199.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8560 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8560 | HTTPS FTP |
-関連構造データ
関連構造データ | 5ujaMC 8559C 5uj9C C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
電子顕微鏡画像生データ | EMPIAR-10813 (タイトル: Cryo-electron microscopy reconstruction of leukotriene C4 bound bovine MRP1 Data size: 938.2 Data #1: Unaligned and uncorrected multiframe movies of bovine leukotriene C4 bound MRP1 [micrographs - multiframe]) |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_8560.map.gz / 形式: CCP4 / 大きさ: 216 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Full map translated into unit cell used for reciprocal space refinement, sharpened with a B-factor of -100 A^2 and a resolution cutoff of 3.34 A | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X: 0.38021 Å / Y: 0.25781 Å / Z: 0.27865 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
-追加マップ: Full map translated into unit cell used for...
ファイル | emd_8560_additional.map | ||||||||||||
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注釈 | Full map translated into unit cell used for reciprocal space refinement, unsharpened | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map 2 translated into unit cell used...
ファイル | emd_8560_half_map_1.map | ||||||||||||
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注釈 | Half map 2 translated into unit cell used for reciprocal space refinement, scaled to PDB coordinates, unsharpened | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map 1 translated into unit cell used...
ファイル | emd_8560_half_map_2.map | ||||||||||||
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注釈 | Half map 1 translated into unit cell used for reciprocal space refinement, scaled to PDB coordinates, unsharpened | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : bovine multidrug resistance protein 1 (MRP1) complexed with leuko...
全体 | 名称: bovine multidrug resistance protein 1 (MRP1) complexed with leukotriene C4 |
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要素 |
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-超分子 #1: bovine multidrug resistance protein 1 (MRP1) complexed with leuko...
超分子 | 名称: bovine multidrug resistance protein 1 (MRP1) complexed with leukotriene C4 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Bos taurus (ウシ) |
分子量 | 理論値: 170 KDa |
-分子 #1: bovine multidrug resistance protein 1 (MRP1),Multidrug resistance...
分子 | 名称: bovine multidrug resistance protein 1 (MRP1),Multidrug resistance-associated protein 1 タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Bos taurus (ウシ) |
分子量 | 理論値: 159.701922 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) ...文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)PNPCPESS ASFLSRI TF WWITGMMVQG YRQPLESTDL WSLNKEDTSE QVVPVLVKNW KKECAKSRKQ PVKIVYSSKD PAKPKGSSKV DVNEEAEA L IVKCPQKERD PSLFKVLYKT FGPYFLMSFL FKAVHDLMMF AGPEILKLLI NFVNDKKAPE WQGYFYTALL FISACLQTL VLHQYFHICF VSGMRIKTAV IGAVYRKALV ITNAARKSST VGEIVNLMSV DAQRFMDLAT YINMIWSAPL QVILALYLLW LNLGPSVLA GVAVMVLMVP LNAVMAMKTK TYQVAHMKSK DNRIKLMNEI LNGIKVLKLY AWELAFKDKV LAIRQEELKV L KKSAYLAA VGTFTWVCTP FLVALSTFAV YVTVDENNIL DAQKAFVSLA LFNILRFPLN ILPMVISSIV QASVSLKRLR VF LSHEDLD PDSIQRRPIK DAGATNSITV KNATFTWARN DPPTLHGITF SVPEGSLVAV VGQVGCGKSS LLSALLAEMD KVE GHVTVK GSVAYVPQQA WIQNISLREN ILFGRQLQER YYKAVVEACA LLPDLEILPS GDRTEIGEKG VNLSGGQKQR VSLA RAVYC DSDVYLLDDP LSAVDAHVGK HIFENVIGPK GLLKNKTRLL VTHAISYLPQ MDVIIVMSGG KISEMGSYQE LLARD GAFA EFLRTYASAE QEQGQPEDGL AGVGGPGKEV KQMENGMLVT DTAGKQMQRQ LSSSSSYSRD VSQHHTSTAE LRKPGP TEE TWKLVEADKA QTGQVKLSVY WDYMKAIGLF ISFLSIFLFL CNHVASLVSN YWLSLWTDDP IVNGTQEHTQ VRLSVYG AL GISQGITVFG YSMAVSIGGI FASRRLHLDL LHNVLRSPIS FFERTPSGNL VNRFSKELDT VDSMIPQVIK MFMGSLFN V IGACIIILLA TPMAAVIIPP LGLIYFFVQR FYVASSRQLK RLESVSRSPV YSHFNETLLG VSVIRAFEEQ ERFIRQSDL KVDENQKAYY PSIVANRWLA VRLECVGNCI VLFASLFAVI SRHSLSAGLV GLSVSYSLQV TTYLNWLVRM SSEMETNIVA VERLKEYSE TEKEAPWQIQ DMAPPKDWPQ VGRVEFRDYG LRYREDLDLV LKHINVTIDG GEKVGIVGRT GAGKSSLTLG L FRIKESAE GEIIIDDINI AKIGLHDLRF KITIIPQDPV LFSGSLRMNL DPFSQYSDEE VWTSLELAHL KGFVSALPDK LN HECAEGG ENLSVGQRQL VCLARALLRK TKILVLDEAT AAVDLETDDL IQSTIRTQFD DCTVLTIAHR LNTIMDYTRV IVL DKGEIQ EWGSPSDLLQ QRGLFYSMAK DSGLVSNSLE VLFQ UniProtKB: Multidrug resistance-associated protein 1 |
-分子 #2: (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-...
分子 | 名称: (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-( 2-hydroxy-2-oxoethylamino)-3-oxidanylidene-propyl]sulfanyl-5-oxidanyl- ...名称: (5~{S},6~{R},7~{E},9~{E},11~{Z},14~{Z})-6-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-( 2-hydroxy-2-oxoethylamino)-3-oxidanylidene-propyl]sulfanyl-5-oxidanyl-icosa-7,9,11,14-tetraenoic acid タイプ: ligand / ID: 2 / コピー数: 1 / 式: LTX |
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分子量 | 理論値: 625.774 Da |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 4.65 mg/mL | ||||||||||||||||||
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緩衝液 | pH: 8 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 400-mesh Au Holey Carbon Grids 材質: GOLD / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY ARRAY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 12 sec. / 前処理 - 雰囲気: AIR | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 295 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 70.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.4 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm 倍率(公称値): 37000 |
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 |
温度 | 最低: 80.0 K / 最高: 100.0 K |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - サイズ - 横: 3710 pixel / デジタル化 - サイズ - 縦: 3838 pixel / デジタル化 - 画像ごとのフレーム数: 1-50 / 撮影したグリッド数: 1 / 実像数: 2302 / 平均露光時間: 7.0 sec. / 平均電子線量: 84.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 203732 |
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初期モデル | モデルのタイプ: OTHER / 詳細: Generated from ISAC and VIPER in the SPARX suite |
初期 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION (ver. 1.4) |
最終 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: FREALIGN |
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 3.34 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: FREALIGN / 使用した粒子像数: 203732 |
-原子モデル構築 1
精密化 | 空間: RECIPROCAL / プロトコル: AB INITIO MODEL |
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得られたモデル | PDB-5uja: |