+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-40460 | ||||||||||||
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タイトル | Cryo-EM map of human cardiac sodium calcium exchanger NCX1 in apo, inactivated state (group I in the presence of 0.5mM Ca2+) | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | Na/Ca exchanger / sodium calcium exchanger / TRANSPORT PROTEIN | ||||||||||||
機能・相同性 | 機能・相同性情報 relaxation of smooth muscle / vascular associated smooth muscle contraction / calcium ion export / regulation of cell communication by electrical coupling / calcium:sodium antiporter activity / membrane depolarization during cardiac muscle cell action potential / regulation of the force of heart contraction / sodium ion export across plasma membrane / negative regulation of protein serine/threonine kinase activity / sodium ion import across plasma membrane ...relaxation of smooth muscle / vascular associated smooth muscle contraction / calcium ion export / regulation of cell communication by electrical coupling / calcium:sodium antiporter activity / membrane depolarization during cardiac muscle cell action potential / regulation of the force of heart contraction / sodium ion export across plasma membrane / negative regulation of protein serine/threonine kinase activity / sodium ion import across plasma membrane / intracellular sodium ion homeostasis / calcium ion import / regulation of cardiac muscle contraction by calcium ion signaling / cardiac muscle cell development / calcium ion transport into cytosol / Sodium/Calcium exchangers / calcium ion transmembrane import into cytosol / relaxation of cardiac muscle / cell communication by electrical coupling involved in cardiac conduction / Reduction of cytosolic Ca++ levels / ankyrin binding / negative regulation of cytosolic calcium ion concentration / cellular response to caffeine / positive regulation of the force of heart contraction / intercalated disc / sodium ion transmembrane transport / calcium ion import across plasma membrane / regulation of cardiac conduction / calcium ion homeostasis / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / positive regulation of bone mineralization / monoatomic ion transport / cardiac muscle contraction / axon terminus / Ion homeostasis / T-tubule / cytoskeletal protein binding / response to muscle stretch / regulation of heart rate / muscle contraction / cell periphery / calcium ion transmembrane transport / sarcolemma / Z disc / cellular response to reactive oxygen species / intracellular calcium ion homeostasis / postsynapse / regulation of gene expression / transmembrane transporter binding / postsynaptic density / calmodulin binding / axon / neuronal cell body / synapse / calcium ion binding / dendrite / nucleoplasm / plasma membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | ||||||||||||
データ登録者 | Xue J / Jiang Y | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1. 著者: Jing Xue / Weizhong Zeng / Yan Han / Scott John / Michela Ottolia / Youxing Jiang / 要旨: Na/Ca exchangers (NCX) transport Ca in or out of cells in exchange for Na. They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca homeostasis. Although extensively ...Na/Ca exchangers (NCX) transport Ca in or out of cells in exchange for Na. They are ubiquitously expressed and play an essential role in maintaining cytosolic Ca homeostasis. Although extensively studied, little is known about the global structural arrangement of eukaryotic NCXs and the structural mechanisms underlying their regulation by various cellular cues including cytosolic Na and Ca. Here we present the cryo-EM structures of human cardiac NCX1 in both inactivated and activated states, elucidating key structural elements important for NCX ion exchange function and its modulation by cytosolic Ca and Na. We demonstrate that the interactions between the ion-transporting transmembrane (TM) domain and the cytosolic regulatory domain define the activity of NCX. In the inward-facing state with low cytosolic [Ca], a TM-associated four-stranded β-hub mediates a tight packing between the TM and cytosolic domains, resulting in the formation of a stable inactivation assembly that blocks the TM movement required for ion exchange function. Ca binding to the cytosolic second Ca-binding domain (CBD2) disrupts this inactivation assembly which releases its constraint on the TM domain, yielding an active exchanger. Thus, the current NCX1 structures provide an essential framework for the mechanistic understanding of the ion transport and cellular regulation of NCX family proteins. | ||||||||||||
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_40460.map.gz | 168.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-40460-v30.xml emd-40460.xml | 15.3 KB 15.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_40460_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
画像 | emd_40460.png | 67.1 KB | ||
Filedesc metadata | emd-40460.cif.gz | 5.3 KB | ||
その他 | emd_40460_half_map_1.map.gz emd_40460_half_map_2.map.gz | 165.4 MB 165.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-40460 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-40460 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_40460_validation.pdf.gz | 912.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_40460_full_validation.pdf.gz | 911.6 KB | 表示 | |
XML形式データ | emd_40460_validation.xml.gz | 20 KB | 表示 | |
CIF形式データ | emd_40460_validation.cif.gz | 25.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40460 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-40460 | 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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「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_40460.map.gz / 形式: CCP4 / 大きさ: 178 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: 0.83 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
-ハーフマップ: #2
ファイル | emd_40460_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_40460_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 : human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
全体 | 名称: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) and bound Fab fragment |
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要素 |
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-超分子 #1: human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
超分子 | 名称: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) and bound Fab fragment タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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-超分子 #2: human cardiac sodium calcium exchanger NCX1 in apo, inactivated s...
超分子 | 名称: human cardiac sodium calcium exchanger NCX1 in apo, inactivated state ( group I in the presence of 0.5mM Ca2+) タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-超分子 #3: antibody Fab fragment
超分子 | 名称: antibody Fab fragment / タイプ: complex / ID: 3 / 親要素: 1 |
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由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
-分子 #1: human cardiac sodium calcium exchanger NCX1
分子 | 名称: human cardiac sodium calcium exchanger NCX1 / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST ...文字列: MYNMRRLSLS PTFSMGFHLL VTVSLLFSHV DHVIAETEME GEGNETGECT GSYYCKKGVI LPIWEPQDPS FGDKIARATV YFVAMVYMFL GVSIIADRFM SSIEVITSQE KEITIKKPNG ETTKTTVRIW NETVSNLTLM ALGSSAPEIL LSVIEVCGHN FTAGDLGPST IVGSAAFNMF IIIALCVYVV PDGETRKIKH LRVFFVTAAW SIFAYTWLYI ILSVISPGVV EVWEGLLTFF FFPICVVFAW VADRRLLFYK YVYKRYRAGK QRGMIIEHEG DRPSSKTEIE MDGKVVNSHV ENFLDGALVL EVDERDQDDE EARREMARIL KELKQKHPDK EIEQLIELAN YQVLSQQQKS RAFYRIQATR LMTGATENDP VSKIFFEQGT YQCLENCGTV ALTIIRRGGD LTNTVFVDFR TEDGTANAGS DYEFTEGTVV FKPGDTQKEI RVGIIDDDIF EEDENFLVHL SNVKVSSEAS EDGILEANHV STLACLGSPS TATVTIFDDD HAGIFTFEEP VTHVSESIGI MEVKVLRTSG ARGNVIVPYK TIEGTARGGG EDFEDTCGEL EFQNDEIVKT ISVKVIDDEE YEKNKTFFLE IGEPRLVEMS EKKALLLNEL GGFTITGKYL FGQPVFRKVH AREHPILSTV ITIADEYDDK QPLTSKEEEE RRIAEMGRPI LGEHTKLEVI IEESYEFKST VDKLIKKTNL ALVVGTNSWR EQFIEAITVS AGEDDDDDEC GEEKLPSCFD YVMHFLTVFW KVLFAFVPPT EYWNGWACFI VSILMIGLLT AFIGDLASHF GCTIGLKDSV TAVVFVALGT SVPDTFASKV AATQDQYADA SIGNVTGSNA VNVFLGIGVA WSIAAIYHAA NGEQFKVSPG TLAFSVTLFT IFAFINVGVL LYRRRPEIGG ELGGPRTAKL LTSCLFVLLW LLYIFFSSLE AYCHIKGF UniProtKB: Sodium/calcium exchanger 1 |
-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: 7.4 |
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凍結 | 凍結剤: ETHANE / 装置: FEI VITROBOT MARK IV |
-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 K3 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
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: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |