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	Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.
ジャーナル・号・ページ	Nat Commun, Vol. 15, Issue 1, Page 6654, Year 2024
掲載日	2024年8月6日
著者	Yangzhuoqun Wan / Shuangshuang Guo / Wenxuan Zhen / Lizhen Xu / Xiaoying Chen / Fangyue Liu / Yi Shen / Shuangshuang Liu / Lidan Hu / Xinyan Wang / Fengcan Ye / Qinrui Wang / Han Wen / Fan Yang /
PubMed 要旨	The ClC-3 chloride/proton exchanger is both physiologically and pathologically critical, as it is potentiated by ATP to detect metabolic energy level and point mutations in ClC-3 lead to severe ...The ClC-3 chloride/proton exchanger is both physiologically and pathologically critical, as it is potentiated by ATP to detect metabolic energy level and point mutations in ClC-3 lead to severe neurodegenerative diseases in human. However, why this exchanger is differentially modulated by ATP, ADP or AMP and how mutations caused gain-of-function remains largely unknow. Here we determine the high-resolution structures of dimeric wildtype ClC-3 in the apo state and in complex with ATP, ADP and AMP, and the disease-causing I607T mutant in the apo and ATP-bounded state by cryo-electron microscopy. In combination with patch-clamp recordings and molecular dynamic simulations, we reveal how the adenine nucleotides binds to ClC-3 and changes in ion occupancy between apo and ATP-bounded state. We further observe I607T mutation induced conformational changes and augments in current. Therefore, our study not only lays the structural basis of adenine nucleotides regulation in ClC-3, but also clearly indicates the target region for drug discovery against ClC-3 mediated neurodegenerative diseases.
リンク	Nat Commun / PubMed:39107281 / PubMed Central
手法	EM (単粒子)
解像度	2.98 - 4.04 Å
構造データ	36200 8jev EMDB-36200, PDB-8jev: Cryo-EM structure of apo state mClC-3 手法: EM (単粒子) / 解像度: 3.06 Å 36236 8jgj EMDB-36236, PDB-8jgj: Cryo-EM structure of mClC-3 with ATP 手法: EM (単粒子) / 解像度: 3.3 Å 36237 8jgk EMDB-36237, PDB-8jgk: Cryo-EM structure of mClC-3 with ADP 手法: EM (単粒子) / 解像度: 4.04 Å 36238 8jgl EMDB-36238, PDB-8jgl: Cryo-EM structure of mClC-3 with AMP 手法: EM (単粒子) / 解像度: 3.14 Å 36245 8jgs EMDB-36245, PDB-8jgs: Cryo-EM structure of apo state mClC-3_I607T 手法: EM (単粒子) / 解像度: 3.96 Å 36246 8jgv EMDB-36246, PDB-8jgv: Cryo-EM structure of mClC-3_I607T with ATP 手法: EM (単粒子) / 解像度: 2.98 Å
化合物	ChemComp-CL: Unknown entry ChemComp-HOH: WATER ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, エネルギー貯蔵分子YM ChemComp-ADP: ADENOSINE-5'-DIPHOSPHATE / ADP, エネルギー貯蔵分子YM ChemComp-AMP: ADENOSINE MONOPHOSPHATE / AMP*YM
由来	mus musculus (ハツカネズミ)
キーワード	MEMBRANE PROTEIN