+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-25092 | |||||||||
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タイトル | Human NKCC1 state Fu-II | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | furosemide (フロセミド) / loop diuretic / diuretic / sodium (ナトリウム) / potassium (カリウム) / chloride (塩化物) / co-transporter / CTD / NKCC1 / MEMBRANE PROTEIN (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 positive regulation of cell volume / positive regulation of aspartate secretion / transepithelial ammonium transport / regulation of matrix metallopeptidase secretion / cell body membrane / inorganic anion import across plasma membrane / inorganic cation import across plasma membrane / chloride:monoatomic cation symporter activity / metal ion transmembrane transporter activity / sodium:potassium:chloride symporter activity ...positive regulation of cell volume / positive regulation of aspartate secretion / transepithelial ammonium transport / regulation of matrix metallopeptidase secretion / cell body membrane / inorganic anion import across plasma membrane / inorganic cation import across plasma membrane / chloride:monoatomic cation symporter activity / metal ion transmembrane transporter activity / sodium:potassium:chloride symporter activity / transepithelial chloride transport / potassium ion transmembrane transporter activity / Cation-coupled Chloride cotransporters / ammonium transmembrane transport / sodium ion homeostasis / intracellular chloride ion homeostasis / negative regulation of vascular wound healing / chloride ion homeostasis / cellular response to potassium ion / intracellular potassium ion homeostasis / cell projection membrane / ammonium channel activity / intracellular sodium ion homeostasis / sodium ion import across plasma membrane / potassium ion homeostasis / T cell chemotaxis / cellular response to chemokine / hyperosmotic response / cell volume homeostasis / gamma-aminobutyric acid signaling pathway / regulation of spontaneous synaptic transmission / maintenance of blood-brain barrier / potassium ion import across plasma membrane / transport across blood-brain barrier / lateral plasma membrane / sodium ion transmembrane transport / monoatomic ion transport / chloride transmembrane transport / basal plasma membrane / cell projection / cell periphery / Hsp90 protein binding / cytoplasmic vesicle membrane / extracellular vesicle / cell body / protein-folding chaperone binding / basolateral plasma membrane / neuron projection / apical plasma membrane / neuronal cell body / protein kinase binding / extracellular exosome / 生体膜 / 細胞膜 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.87 Å | |||||||||
データ登録者 | Moseng MA | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Sci Adv / 年: 2022 タイトル: Inhibition mechanism of NKCC1 involves the carboxyl terminus and long-range conformational coupling. 著者: Mitchell A Moseng / Chih-Chia Su / Kerri Rios / Meng Cui / Meinan Lyu / Przemyslaw Glaza / Philip A Klenotic / Eric Delpire / Edward W Yu / 要旨: The Na-K-2Cl cotransporter-1 (NKCC1) is an electroneutral Na-dependent transporter responsible for simultaneously translocating Na, K, and Cl ions into cells. In human tissue, NKCC1 plays a critical ...The Na-K-2Cl cotransporter-1 (NKCC1) is an electroneutral Na-dependent transporter responsible for simultaneously translocating Na, K, and Cl ions into cells. In human tissue, NKCC1 plays a critical role in regulating cytoplasmic volume, fluid intake, chloride homeostasis, and cell polarity. Here, we report four structures of human NKCC1 (hNKCC1), both in the absence and presence of loop diuretic (bumetanide or furosemide), using single-particle cryo-electron microscopy. These structures allow us to directly observe various novel conformations of the hNKCC1 dimer. They also reveal two drug-binding sites located at the transmembrane and cytosolic carboxyl-terminal domains, respectively. Together, our findings enable us to delineate an inhibition mechanism that involves a coupled movement between the cytosolic and transmembrane domains of hNKCC1. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_25092.map.gz | 230 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-25092-v30.xml emd-25092.xml | 14.8 KB 14.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_25092_fsc.xml | 13.2 KB | 表示 | FSCデータファイル |
画像 | emd_25092.png | 124.8 KB | ||
マスクデータ | emd_25092_msk_1.map | 244.1 MB | マスクマップ | |
その他 | emd_25092_half_map_1.map.gz emd_25092_half_map_2.map.gz | 226.5 MB 226.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-25092 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25092 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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-マップ
ファイル | ダウンロード / ファイル: emd_25092.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.07 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_25092_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_25092_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_25092_half_map_2.map | ||||||||||||
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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 : NKCC1 with furosemide
全体 | 名称: NKCC1 with furosemide |
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要素 |
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-超分子 #1: NKCC1 with furosemide
超分子 | 名称: NKCC1 with furosemide / 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: Homo sapiens (ヒト) |
-分子 #1: Solute carrier family 12 member 2
分子 | 名称: Solute carrier family 12 member 2 / タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 100.435695 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: GWIKGVLVRC MLNIWGVMLF IRLSWIVGQA GIGLSVLVIM MATVVTTITG LSTSAIATNG FVRGGGAYYL ISRSLGPEFG GAIGLIFAF ANAVAVAMYV VGFAETVVEL LKEHSILMID EINDIRIIGA ITVVILLGIS VAGMEWEAKA QIVLLVILLL A IGDFVIGT ...文字列: GWIKGVLVRC MLNIWGVMLF IRLSWIVGQA GIGLSVLVIM MATVVTTITG LSTSAIATNG FVRGGGAYYL ISRSLGPEFG GAIGLIFAF ANAVAVAMYV VGFAETVVEL LKEHSILMID EINDIRIIGA ITVVILLGIS VAGMEWEAKA QIVLLVILLL A IGDFVIGT FIPLESKKPK GFFGYKSEIF NENFGPDFRE EETFFSVFAI FFPAATGILA GANISGDLAD PQSAIPKGTL LA ILITTLV YVGIAVSVGS CVVRDATGNV NDTIVTELTN CTSAACKLNF DFSSCESSPC SYGLMNNFQV MSMVSGFTPL ISA GIFSAT LSSALASLVS APKIFQALCK DNIYPAFQMF AKGYGKNNEP LRGYILTFLI ALGFILIAEL NVIAPIISNF FLAS YALIN FSVFHASLAK SPGWRPAFKY YNMWISLLGA ILCCIVMFVI NWWAALLTYV IVLGLYIYVT YKKPDVNWGS STQAL TYLN ALQHSIRLSG VEDHVKNFRP QCLVMTGAPN SRPALLHLVH DFTKNVGLMI CGHVHMGPRR QAMKEMSIDQ AKYQRW LIK NKMKAFYAPV HADDLREGAQ YLMQAAGLGR MKPNTLVLGF KKDWLQADMR DVDMYINLFH DAFDIQYGVV VIRLKEG L(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)KQGKN TIDVWWLFDD GGLTL LIPY LLTTKKKWKD CKIRVFIGGK INRIDHDRRA MATLLSKFRI DFSDIMVLGD INTKPKKENI IAFEEIIEPY RLHEDD KEQ DIADKMKEDE PWRITDNELE LYKTKTYRQI RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPI LL VRGNHQSVLT F |
-分子 #2: 5-(AMINOSULFONYL)-4-CHLORO-2-[(2-FURYLMETHYL)AMINO]BENZOIC ACID
分子 | 名称: 5-(AMINOSULFONYL)-4-CHLORO-2-[(2-FURYLMETHYL)AMINO]BENZOIC ACID タイプ: ligand / ID: 2 / コピー数: 2 / 式: FUN |
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分子量 | 理論値: 330.744 Da |
Chemical component information | ChemComp-FUN: |
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-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 | 照射モード: OTHER / 撮影モード: BRIGHT FIELDBright-field microscopy / 最大 デフォーカス(公称値): 5.0 µm / 最小 デフォーカス(公称値): 1.2 µm |
撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 41.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |