+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6baa | ||||||
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タイトル | Cryo-EM structure of the pancreatic beta-cell KATP channel bound to ATP and glibenclamide | ||||||
要素 |
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キーワード | METAL TRANSPORT / KATP / SUR1 / Kir6.2 / sulfonylurea receptor | ||||||
機能・相同性 | 機能・相同性情報 Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade ...Regulation of insulin secretion / ATP sensitive Potassium channels / ABC-family proteins mediated transport / response to resveratrol / ATP-activated inward rectifier potassium channel activity / inward rectifying potassium channel / cell body fiber / sulfonylurea receptor activity / ventricular cardiac muscle tissue development / CAMKK-AMPK signaling cascade / voltage-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / inward rectifier potassium channel activity / ATPase-coupled monoatomic cation transmembrane transporter activity / nervous system process / regulation of monoatomic ion transmembrane transport / inorganic cation transmembrane transport / ankyrin binding / Ion homeostasis / response to ATP / response to testosterone / voltage-gated potassium channel activity / potassium ion import across plasma membrane / action potential / regulation of insulin secretion / potassium channel activity / intercalated disc / axolemma / ABC-type transporter activity / negative regulation of insulin secretion / potassium ion transmembrane transport / T-tubule / heat shock protein binding / positive regulation of protein localization to plasma membrane / potassium ion transport / acrosomal vesicle / regulation of membrane potential / response to ischemia / determination of adult lifespan / cellular response to glucose stimulus / sarcolemma / cellular response to nicotine / glucose metabolic process / nuclear envelope / response to estradiol / cellular response to tumor necrosis factor / presynaptic membrane / transmembrane transporter binding / endosome / response to hypoxia / response to xenobiotic stimulus / neuronal cell body / glutamatergic synapse / apoptotic process / ATP hydrolysis activity / ATP binding / plasma membrane 類似検索 - 分子機能 | ||||||
生物種 | Rattus norvegicus (ドブネズミ) Cricetus cricetus (クロハラハムスクー) | ||||||
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: 3.63 Å | ||||||
データ登録者 | Martin, G.M. / Yoshioka, C. / Shyng, S.L. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Elife / 年: 2017 タイトル: Anti-diabetic drug binding site in a mammalian K channel revealed by Cryo-EM. 著者: Gregory M Martin / Balamurugan Kandasamy / Frank DiMaio / Craig Yoshioka / Show-Ling Shyng / 要旨: Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been ...Sulfonylureas are anti-diabetic medications that act by inhibiting pancreatic K channels composed of SUR1 and Kir6.2. The mechanism by which these drugs interact with and inhibit the channel has been extensively investigated, yet it remains unclear where the drug binding pocket resides. Here, we present a cryo-EM structure of a hamster SUR1/rat Kir6.2 channel bound to a high-affinity sulfonylurea drug glibenclamide and ATP at 3.63 Å resolution, which reveals unprecedented details of the ATP and glibenclamide binding sites. Importantly, the structure shows for the first time that glibenclamide is lodged in the transmembrane bundle of the SUR1-ABC core connected to the first nucleotide binding domain near the inner leaflet of the lipid bilayer. Mutation of residues predicted to interact with glibenclamide in our model led to reduced sensitivity to glibenclamide. Our structure provides novel mechanistic insights of how sulfonylureas and ATP interact with the K channel complex to inhibit channel activity. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6baa.cif.gz | 1 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6baa.ent.gz | 832.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6baa.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ba/6baa ftp://data.pdbj.org/pub/pdb/validation_reports/ba/6baa | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 43645.719 Da / 分子数: 4 / 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: Kcnj11 / 細胞株 (発現宿主): INS-1 / 発現宿主: Rattus norvegicus (ドブネズミ) / 参照: UniProt: P70673 #2: タンパク質 | 分子量: 177333.578 Da / 分子数: 4 / 由来タイプ: 組換発現 由来: (組換発現) Cricetus cricetus (クロハラハムスクー) 遺伝子: ABCC8, SUR / 発現宿主: Rattus norvegicus (ドブネズミ) / 参照: UniProt: Q09427 #3: 化合物 | ChemComp-ATP / #4: 化合物 | ChemComp-GBM / |
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-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 |
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分子量 | 値: 0.95 MDa / 実験値: NO | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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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 |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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対称性 | 点対称性: C4 (4回回転対称) |
3次元再構成 | 解像度: 3.63 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 59417 / 対称性のタイプ: POINT |