登録情報 データベース : PDB / ID : 6pz9 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and repaglinide 要素ATP-binding cassette sub-family C member 8 ATP-sensitive inward rectifier potassium channel 11 詳細キーワード MEMBRANE PROTEIN / KATP / SUR1 / RPG機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / regulation of monoatomic ion transmembrane transport / nervous system process / inorganic cation transmembrane transport / ankyrin binding / action potential / response to ATP / Ion homeostasis / response to testosterone / voltage-gated potassium channel activity / potassium channel activity / potassium ion import across plasma membrane / regulation of insulin secretion / intercalated disc / axolemma / negative regulation of insulin secretion / ABC-type transporter activity / potassium ion transmembrane transport / T-tubule / heat shock protein binding / acrosomal vesicle / response to ischemia / regulation of membrane potential / determination of adult lifespan / cellular response to glucose stimulus / positive regulation of protein localization to plasma membrane / potassium ion transport / sarcolemma / cellular response to nicotine / glucose metabolic process / response to estradiol / nuclear envelope / presynaptic membrane / cellular response to tumor necrosis factor / transmembrane transporter binding / response to hypoxia / endosome / 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 Potassium channel, inwardly rectifying, Kir6.2 / ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / Potassium channel, inwardly rectifying, transmembrane domain / Inward rectifier potassium channel transmembrane domain / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / Inward rectifier potassium channel, C-terminal / Inward rectifier potassium channel C-terminal domain / ABC transporter transmembrane region ... Potassium channel, inwardly rectifying, Kir6.2 / ATP-binding cassette subfamily C member 8 / Sulphonylurea receptor / Potassium channel, inwardly rectifying, transmembrane domain / Inward rectifier potassium channel transmembrane domain / Potassium channel, inwardly rectifying, Kir, cytoplasmic / Potassium channel, inwardly rectifying, Kir / Inward rectifier potassium channel, C-terminal / Inward rectifier potassium channel C-terminal domain / ABC transporter transmembrane region / ABC transporter type 1, transmembrane domain / ABC transporter integral membrane type-1 fused domain profile. / ABC transporter type 1, transmembrane domain superfamily / ABC transporter-like, conserved site / ABC transporters family signature. / ABC transporter / ABC transporter-like, ATP-binding domain / ATP-binding cassette, ABC transporter-type domain profile. / Immunoglobulin E-set / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase 類似検索 - ドメイン・相同性 ADENOSINE-5'-TRIPHOSPHATE / Repaglinide / ATP-sensitive inward rectifier potassium channel 11 / ATP-binding cassette sub-family C member 8 類似検索 - 構成要素生物種 Cricetus cricetus (クロハラハムスクー)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 : 3.65 Å 詳細データ登録者 Shyng, S.L. / Yoshioka, C. / Martin, G.M. / Sung, M.W. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK) 米国
引用ジャーナル : Elife / 年 : 2019タイトル : Mechanism of pharmacochaperoning in a mammalian K channel revealed by cryo-EM.著者 : Gregory M Martin / Min Woo Sung / Zhongying Yang / Laura M Innes / Balamurugan Kandasamy / Larry L David / Craig Yoshioka / Show-Ling Shyng / 要旨 : ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β- ... ATP-sensitive potassium (K) channels composed of a pore-forming Kir6.2 potassium channel and a regulatory ABC transporter sulfonylurea receptor 1 (SUR1) regulate insulin secretion in pancreatic β-cells to maintain glucose homeostasis. Mutations that impair channel folding or assembly prevent cell surface expression and cause congenital hyperinsulinism. Structurally diverse K inhibitors are known to act as pharmacochaperones to correct mutant channel expression, but the mechanism is unknown. Here, we compare cryoEM structures of a mammalian K channel bound to pharmacochaperones glibenclamide, repaglinide, and carbamazepine. We found all three drugs bind within a common pocket in SUR1. Further, we found the N-terminus of Kir6.2 inserted within the central cavity of the SUR1 ABC core, adjacent the drug binding pocket. The findings reveal a common mechanism by which diverse compounds stabilize the Kir6.2 N-terminus within SUR1's ABC core, allowing it to act as a firm 'handle' for the assembly of metastable mutant SUR1-Kir6.2 complexes. 履歴 登録 2019年7月31日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2019年8月14日 Provider : repository / タイプ : Initial release改定 1.1 2019年12月25日 Group : Author supporting evidence / カテゴリ : pdbx_audit_support / Item : _pdbx_audit_support.funding_organization改定 1.2 2020年10月7日 Group : Database references / カテゴリ : citation / Item : _citation.title改定 1.3 2024年3月20日 Group : Data collection / Database references / Refinement descriptionカテゴリ : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession ... _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type
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