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基本情報
登録情報 | データベース: EMDB / ID: EMD-9230 | |||||||||
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タイトル | Phosphorylated, ATP-bound human cystic fibrosis transmembrane conductance regulator (CFTR) | |||||||||
![]() | 3.2A frealign refined map with -50A2 b-factor sharpening | |||||||||
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![]() | ABC transporter / anion channel / cystic fibrosis / membrane protein / HYDROLASE | |||||||||
機能・相同性 | ![]() positive regulation of voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis ...positive regulation of voltage-gated chloride channel activity / positive regulation of cyclic nucleotide-gated ion channel activity / Sec61 translocon complex binding / channel-conductance-controlling ATPase / intracellularly ATP-gated chloride channel activity / positive regulation of enamel mineralization / transepithelial water transport / RHO GTPases regulate CFTR trafficking / intracellular pH elevation / amelogenesis / chloride channel inhibitor activity / ATPase-coupled inorganic anion transmembrane transporter activity / Golgi-associated vesicle membrane / multicellular organismal-level water homeostasis / membrane hyperpolarization / cholesterol transport / bicarbonate transport / bicarbonate transmembrane transporter activity / vesicle docking involved in exocytosis / chloride channel regulator activity / chloride transmembrane transporter activity / sperm capacitation / chloride channel activity / RHOQ GTPase cycle / cholesterol biosynthetic process / positive regulation of exocytosis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / chloride channel complex / ATPase-coupled transmembrane transporter activity / ABC-type transporter activity / cellular response to cAMP / cellular response to forskolin / chloride transmembrane transport / isomerase activity / response to endoplasmic reticulum stress / establishment of localization in cell / PDZ domain binding / Defective CFTR causes cystic fibrosis / Late endosomal microautophagy / clathrin-coated endocytic vesicle membrane / ABC-family proteins mediated transport / recycling endosome / transmembrane transport / Aggrephagy / Chaperone Mediated Autophagy / recycling endosome membrane / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / early endosome membrane / protein-folding chaperone binding / early endosome / endosome membrane / Ub-specific processing proteases / apical plasma membrane / lysosomal membrane / endoplasmic reticulum membrane / enzyme binding / cell surface / ATP hydrolysis activity / protein-containing complex / ATP binding / membrane / nucleus / 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: 3.2 Å | |||||||||
![]() | Zhang Z / Liu F | |||||||||
![]() | ![]() タイトル: Molecular structure of the ATP-bound, phosphorylated human CFTR. 著者: Zhe Zhang / Fangyu Liu / Jue Chen / ![]() 要旨: The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel important in maintaining proper functions of the lung, pancreas, and intestine. The activity of CFTR is regulated by ...The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel important in maintaining proper functions of the lung, pancreas, and intestine. The activity of CFTR is regulated by ATP and protein kinase A-dependent phosphorylation. To understand the conformational changes elicited by phosphorylation and ATP binding, we present here the structure of phosphorylated, ATP-bound human CFTR, determined by cryoelectron microscopy to 3.2-Å resolution. This structure reveals the position of the R domain after phosphorylation. By comparing the structures of human CFTR and zebrafish CFTR determined under the same condition, we identified common features essential to channel gating. The differences in their structures indicate plasticity permitted in evolution to achieve the same function. Finally, the structure of CFTR provides a better understanding of why the G178R, R352Q, L927P, and G970R/D mutations would impede conformational changes of CFTR and lead to cystic fibrosis. | |||||||||
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: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 72.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 13.1 KB 13.1 KB | 表示 表示 | ![]() |
画像 | ![]() | 49.7 KB | ||
Filedesc metadata | ![]() | 6.6 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 482 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 481.5 KB | 表示 | |
XML形式データ | ![]() | 6.5 KB | 表示 | |
CIF形式データ | ![]() | 7.4 KB | 表示 | |
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「今月の分子」の関連する項目 |
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注釈 | 3.2A frealign refined map with -50A2 b-factor sharpening | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.03 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
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試料の構成要素
-全体 : human cystic fibrosis transmembrane conductance regulator (CFTR)
全体 | 名称: human cystic fibrosis transmembrane conductance regulator (CFTR) |
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要素 |
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-超分子 #1: human cystic fibrosis transmembrane conductance regulator (CFTR)
超分子 | 名称: human cystic fibrosis transmembrane conductance regulator (CFTR) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 168 KDa |
-分子 #1: Cystic fibrosis transmembrane conductance regulator
分子 | 名称: Cystic fibrosis transmembrane conductance regulator / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO / EC番号: ec: 3.6.3.49 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 169.352594 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MQRSPLEKAS VVSKLFFSWT RPILRKGYRQ RLELSDIYQI PSVDSADNLS EKLEREWDRE LASKKNPKLI NALRRCFFWR FMFYGIFLY LGEVTKAVQP LLLGRIIASY DPDNKEERSI AIYLGIGLCL LFIVRTLLLH PAIFGLHHIG MQMRIAMFSL I YKKTLKLS ...文字列: MQRSPLEKAS VVSKLFFSWT RPILRKGYRQ RLELSDIYQI PSVDSADNLS EKLEREWDRE LASKKNPKLI NALRRCFFWR FMFYGIFLY LGEVTKAVQP LLLGRIIASY DPDNKEERSI AIYLGIGLCL LFIVRTLLLH PAIFGLHHIG MQMRIAMFSL I YKKTLKLS SRVLDKISIG QLVSLLSNNL NKFDEGLALA HFVWIAPLQV ALLMGLIWEL LQASAFCGLG FLIVLALFQA GL GRMMMKY RDQRAGKISE RLVITSEMIE NIQSVKAYCW EEAMEKMIEN LRQTELKLTR KAAYVRYFNS SAFFFSGFFV VFL SVLPYA LIKGIILRKI FTTISFCIVL RMAVTRQFPW AVQTWYDSLG AINKIQDFLQ KQEYKTLEYN LTTTEVVMEN VTAF WEEGF GELFEKAKQN NNNRKTSNGD DSLFFSNFSL LGTPVLKDIN FKIERGQLLA VAGSTGAGKT SLLMVIMGEL EPSEG KIKH SGRISFCSQF SWIMPGTIKE NIIFGVSYDE YRYRSVIKAC QLEEDISKFA EKDNIVLGEG GITLSGGQRA RISLAR AVY KDADLYLLDS PFGYLDVLTE KEIFESCVCK LMANKTRILV TSKMEHLKKA DKILILHEGS SYFYGTFSEL QNLQPDF SS KLMGCDSFDQ FSAERRNSIL TETLHRFSLE GDAPVSWTET KKQSFKQTGE FGEKRKNSIL NPINSIRKFS IVQKTPLQ M NGIEEDSDEP LERRLSLVPD SEQGEAILPR ISVISTGPTL QARRRQSVLN LMTHSVNQGQ NIHRKTTAST RKVSLAPQA NLTELDIYSR RLSQETGLEI SEEINEEDLK ECFFDDMESI PAVTTWNTYL RYITVHKSLI FVLIWCLVIF LAEVAASLVV LWLLGNTPL QDKGNSTHSR NNSYAVIITS TSSYYVFYIY VGVADTLLAM GFFRGLPLVH TLITVSKILH HKMLHSVLQA P MSTLNTLK AGGILNRFSK DIAILDDLLP LTIFDFIQLL LIVIGAIAVV AVLQPYIFVA TVPVIVAFIM LRAYFLQTSQ QL KQLESEG RSPIFTHLVT SLKGLWTLRA FGRQPYFETL FHKALNLHTA NWFLYLSTLR WFQMRIEMIF VIFFIAVTFI SIL TTGEGE GRVGIILTLA MNIMSTLQWA VNSSIDVDSL MRSVSRVFKF IDMPTEGKPT KSTKPYKNGQ LSKVMIIENS HVKK DDIWP SGGQMTVKDL TAKYTEGGNA ILENISFSIS PGQRVGLLGR TGSGKSTLLS AFLRLLNTEG EIQIDGVSWD SITLQ QWRK AFGVIPQKVF IFSGTFRKNL DPYEQWSDQE IWKVADEVGL RSVIEQFPGK LDFVLVDGGC VLSHGHKQLM CLARSV LSK AKILLLDQPS AHLDPVTYQI IRRTLKQAFA DCTVILCEHR IEAMLECQQF LVIEENKVRQ YDSIQKLLNE RSLFRQA IS PSDRVKLFPH RNSSKCKSKP QIAALKEETE EEVQDTRLSN SLEVLFQ UniProtKB: Cystic fibrosis transmembrane conductance regulator |
-分子 #2: Piece of Molecule-1
分子 | 名称: Piece of Molecule-1 / タイプ: protein_or_peptide / ID: 2 / 詳細: This is a part of Chain A / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.464797 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK)(UNK)(UNK)(UNK)(UNK)(UNK) (UNK) |
-分子 #3: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 3 / コピー数: 2 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #4: ADENOSINE-5'-TRIPHOSPHATE
分子 | 名称: ADENOSINE-5'-TRIPHOSPHATE / タイプ: ligand / ID: 4 / コピー数: 2 / 式: ATP |
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分子量 | 理論値: 507.181 Da |
Chemical component information | ![]() ChemComp-ATP: |
-分子 #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
分子 | 名称: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate タイプ: ligand / ID: 5 / コピー数: 5 / 式: POV |
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分子量 | 理論値: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-分子 #6: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 6 / コピー数: 1 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-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 | 5 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | 詳細: unspecified |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 298 K / 装置: FEI VITROBOT MARK I |
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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 K2 SUMMIT (4k x 4k) 平均電子線量: 1.51 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
初期モデル | モデルのタイプ: EMDB MAP EMDB ID: |
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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: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 677308 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |