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	The inhibition mechanism of the SUR2A-containing K channel by a regulatory helix.
ジャーナル・号・ページ	Nat Commun, Vol. 14, Issue 1, Page 3608, Year 2023
掲載日	2023年6月17日
著者	Dian Ding / Tianyi Hou / Miao Wei / Jing-Xiang Wu / Lei Chen /
PubMed 要旨	K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing ...K channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing K channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation.
リンク	Nat Commun / PubMed:37330603 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 3.8 Å
構造データ	33563 7y1j EMDB-33563, PDB-7y1j: Structure of SUR2A in complex with Mg-ATP and repaglinide in the inward-facing conformation. 手法: EM (単粒子) / 解像度: 3.0 Å 33564 7y1k EMDB-33564, PDB-7y1k: Structure of SUR2A in complex with Mg-ATP, Mg-ADP and repaglinide in the inward-facing conformation 手法: EM (単粒子) / 解像度: 3.8 Å 33565 7y1l EMDB-33565, PDB-7y1l: Structure of SUR2B in complex with Mg-ATP and repaglinide in the inward-facing conformation 手法: EM (単粒子) / 解像度: 3.73 Å 33566 7y1m EMDB-33566, PDB-7y1m: Structure of SUR2B in complex with Mg-ATP, Mg-ADP, and repaglinide in the inward-facing conformation 手法: EM (単粒子) / 解像度: 3.57 Å 33567 7y1n EMDB-33567, PDB-7y1n: Structure of SUR2B in complex with Mg-ATP, Mg-ADP, and repaglinide in the partially occluded state 手法: EM (単粒子) / 解像度: 3.61 Å
化合物	ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子YM ChemComp-MG: Unknown entry / マグネシウムジカチオン ChemComp-BJX: Repaglinide / レパグリニド / 薬剤YM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP / ADP, エネルギー貯蔵分子*YM
由来	rattus norvegicus (ドブネズミ)
キーワード	MEMBRANE PROTEIN / SUR2A / ABC transporter / repaglinide / SUR2B