EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure of an open K channel reveals tandem PIP binding sites mediating the Kir6.2 and SUR1 regulatory interface.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 2502, Year 2024
掲載日	2024年3月20日
著者	Camden M Driggers / Yi-Ying Kuo / Phillip Zhu / Assmaa ElSheikh / Show-Ling Shyng /
PubMed 要旨	ATP-sensitive potassium (K) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K ...ATP-sensitive potassium (K) channels, composed of four pore-lining Kir6.2 subunits and four regulatory sulfonylurea receptor 1 (SUR1) subunits, control insulin secretion in pancreatic β-cells. K channel opening is stimulated by PIP and inhibited by ATP. Mutations that increase channel opening by PIP reduce ATP inhibition and cause neonatal diabetes. Although considerable evidence has implicated a role for PIP in K channel function, previously solved open-channel structures have lacked bound PIP, and mechanisms by which PIP regulates K channels remain unresolved. Here, we report the cryoEM structure of a K channel harboring the neonatal diabetes mutation Kir6.2-Q52R, in the open conformation, bound to amphipathic molecules consistent with natural C18:0/C20:4 long-chain PI(4,5)P at two adjacent binding sites between SUR1 and Kir6.2. The canonical PIP binding site is conserved among PIP-gated Kir channels. The non-canonical PIP binding site forms at the interface of Kir6.2 and SUR1. Functional studies demonstrate both binding sites determine channel activity. Kir6.2 pore opening is associated with a twist of the Kir6.2 cytoplasmic domain and a rotation of the N-terminal transmembrane domain of SUR1, which widens the inhibitory ATP binding pocket to disfavor ATP binding. The open conformation is particularly stabilized by the Kir6.2-Q52R residue through cation-π bonding with SUR1-W51. Together, these results uncover the cooperation between SUR1 and Kir6.2 in PIP binding and gating, explain the antagonistic regulation of K channels by PIP and ATP, and provide a putative mechanism by which Kir6.2-Q52R stabilizes an open channel to cause neonatal diabetes.
リンク	Nat Commun / PubMed:38509107 / PubMed Central
手法	EM (単粒子)
解像度	2.9 - 6.9 Å
構造データ	41277 8ti1 EMDB-41277, PDB-8ti1: Cryo-EM structure of a SUR1/Kir6.2-Q52R ATP-sensitive potassium channel in the presence of PIP2 in the open conformation 手法: EM (単粒子) / 解像度: 2.9 Å 41278 8ti2 EMDB-41278, PDB-8ti2: Cryo-EM structure of a SUR1/Kir6.2-Q52R ATP-sensitive potassium channel in the presence of PIP2 in the open conformation 手法: EM (単粒子) / 解像度: 3.28 Å EMDB-43766: Kir6.2-Q52R/SUR1 apo closed channel 手法: EM (単粒子) / 解像度: 6.9 Å
化合物	ChemComp-PT5: [(2R)-1-octadecanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phospho / リン脂質YM / ホスファチジルイノシトール4,5-ビスリン酸 ChemComp-K: Unknown entry / カリウムカチオン ChemComp-PEF: DI-PALMITOYL-3-SN-PHOSPHATIDYLETHANOLAMINE / DPPE / リン脂質YM / ホスファチジルエタノールアミン ChemComp-P5S: O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine / O-(1-O,2-O-ジステアロイル-L-グリセロ-3-ホスホ)セリン / ホスファチジルセリン ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-HOH: WATER / 水
由来	rattus norvegicus (ドブネズミ) mesocricetus auratus (ゴールデンハムスター)
キーワード	TRANSPORT PROTEIN (運搬体タンパク質) / ATP-sensitive potassium channel (ATP感受性カリウムチャネル) / KATP channel (ATP感受性カリウムチャネル) / SUR1 / Kir6.2-Q52R / potassium transport / metabolic sensor / diabetes (糖尿病) / phospholipid binding (リン脂質) / PIP2 (ホスファチジルイノシトール4,5-ビスリン酸)