+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7vlr | ||||||||||||
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タイトル | Structure of SUR2B in complex with Mg-ATP/ADP | ||||||||||||
要素 | Isoform SUR2B of ATP-binding cassette sub-family C member 9 | ||||||||||||
キーワード | MEMBRANE PROTEIN / SUR2B / ABC transporter | ||||||||||||
機能・相同性 | 機能・相同性情報 vascular process in circulatory system / substrate-dependent cell migration, cell contraction / oxygen metabolic process / reactive oxygen species biosynthetic process / response to decreased oxygen levels / ATP sensitive Potassium channels / response to peptide / ABC-family proteins mediated transport / inward rectifying potassium channel / sulfonylurea receptor activity ...vascular process in circulatory system / substrate-dependent cell migration, cell contraction / oxygen metabolic process / reactive oxygen species biosynthetic process / response to decreased oxygen levels / ATP sensitive Potassium channels / response to peptide / ABC-family proteins mediated transport / inward rectifying potassium channel / sulfonylurea receptor activity / response to hydrogen sulfide / response to potassium ion / cardiac conduction / circulatory system development / response to oxygen levels / cellular response to potassium ion / coronary vasculature development / ATPase-coupled monoatomic cation transmembrane transporter activity / cellular response to chemical stress / cardiac muscle cell contraction / regulation of potassium ion transmembrane transport / inorganic cation transmembrane transport / blood circulation / syntaxin binding / cellular respiration / response to stress / heterocyclic compound binding / cellular response to ATP / Ion homeostasis / response to ATP / action potential / blood vessel development / potassium ion import across plasma membrane / monoatomic cation transmembrane transport / fatty acid oxidation / ATPase-coupled transmembrane transporter activity / potassium channel activity / ABC-type transporter activity / potassium channel regulator activity / heart morphogenesis / ATP metabolic process / skeletal muscle tissue development / T-tubule / potassium ion transmembrane transport / negative regulation of blood pressure / sarcomere / cellular response to calcium ion / blood vessel diameter maintenance / acrosomal vesicle / regulation of membrane potential / response to activity / mitochondrion organization / potassium ion transport / response to hydrogen peroxide / transmembrane transport / sarcolemma / regulation of blood pressure / response to estrogen / vasodilation / MAPK cascade / cellular response to xenobiotic stimulus / heart development / gene expression / fibroblast proliferation / defense response to virus / transmembrane transporter binding / response to hypoxia / response to xenobiotic stimulus / protein-containing complex binding / negative regulation of apoptotic process / regulation of transcription by RNA polymerase II / ATP hydrolysis activity / protein-containing complex / mitochondrion / ATP binding / identical protein binding / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | ||||||||||||
生物種 | Rattus norvegicus (ドブネズミ) | ||||||||||||
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: 3.4 Å | ||||||||||||
データ登録者 | Chen, L. / Ding, D. | ||||||||||||
資金援助 | 中国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Structural identification of vasodilator binding sites on the SUR2 subunit. 著者: Dian Ding / Jing-Xiang Wu / Xinli Duan / Songling Ma / Lipeng Lai / Lei Chen / 要旨: ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by ...ATP-sensitive potassium channels (K), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing K channels by class of small molecule drugs known as K openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, K openers could be used to treat cardiovascular diseases. However, where these vasodilators bind to K and how they activate the channel remains elusive. Here, we present cryo-EM structures of SUR2A and SUR2B subunits in complex with Mg-nucleotides and P1075 or levcromakalim, two chemically distinct K openers that are specific to SUR2. Both P1075 and levcromakalim bind to a common site in the transmembrane domain (TMD) of the SUR2 subunit, which is between TMD1 and TMD2 and is embraced by TM10, TM11, TM12, TM14, and TM17. These K openers synergize with Mg-nucleotides to stabilize SUR2 in the NBD-dimerized occluded state to activate the channel. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7vlr.cif.gz | 244.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7vlr.ent.gz | 186.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7vlr.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 | 7vlr_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7vlr_full_validation.pdf.gz | 1.4 MB | 表示 | |
XML形式データ | 7vlr_validation.xml.gz | 39.8 KB | 表示 | |
CIF形式データ | 7vlr_validation.cif.gz | 58.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vl/7vlr ftp://data.pdbj.org/pub/pdb/validation_reports/vl/7vlr | 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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-要素
#1: タンパク質 | 分子量: 174488.562 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Abcc9, Sur2 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q63563 | ||||
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#2: 化合物 | ChemComp-Y01 / | ||||
#3: 化合物 | ChemComp-ADP / | ||||
#4: 化合物 | #5: 化合物 | ChemComp-ATP / | 研究の焦点であるリガンドがあるか | Y | |
-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: ATP-binding cassette sub-family C member 9, isoform B タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 値: 174 kDa/nm / 実験値: NO |
由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.5 |
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 / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 1500 nm |
撮影 | 電子線照射量: 52 e/Å2 / 検出モード: SUPER-RESOLUTION 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 | 名称: cryoSPARC / バージョン: 3.1.0 / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
対称性 | 点対称性: C1 (非対称) |
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 36180 / 対称性のタイプ: POINT |