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	Physiological temperature drives TRPM4 ligand recognition and gating.
ジャーナル・号・ページ	Nature, Vol. 630, Issue 8016, Page 509-515, Year 2024
掲載日	2024年5月15日
著者	Jinhong Hu / Sung Jin Park / Tyler Walter / Ian J Orozco / Garrett O'Dea / Xinyu Ye / Juan Du / Wei Lü /
PubMed 要旨	Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity. However, its impact is often overlooked in biophysical studies that are typically ...Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity. However, its impact is often overlooked in biophysical studies that are typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. Here we demonstrate temperature-dependent changes in the structure and function of TRPM4, a temperature-sensitive Ca-activated ion channel. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we identified a 'warm' conformation that is distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca-binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (a positive modulator) and ATP (an inhibitor), bind to different locations of TRPM4 at physiological temperatures than at lower temperatures, and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperatures, revealing the channel opening that is not observed at lower temperatures. Our study provides an example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperatures. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes.
リンク	Nature / PubMed:38750366 / PubMed Central
手法	EM (単粒子)
解像度	3.0 - 4.4 Å
構造データ	44360 9b8w EMDB-44360, PDB-9b8w: Cryo-EM structure of the human TRPM4 in complex with calcium at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.1 Å 44361 9b8x EMDB-44361, PDB-9b8x: Cryo-EM structure of the human TRPM4 channel subunit in complex with calcium 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.0 Å 44362 9b8y EMDB-44362, PDB-9b8y: Cryo-EM structure of the human TRPM4 channel in complex with calcium and decavanadate at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.2 Å 44363 9b8z EMDB-44363, PDB-9b8z: Cryo-EM structure of the human TRPM4 channel subunit in complex with calcium and decavanadate at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.4 Å 44364 9b90 EMDB-44364, PDB-9b90: Cryo-EM structure of the human TRPM4 channel in complex with calcium and ATP at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.4 Å 44365 9b91 EMDB-44365, PDB-9b91: Cryo-EM structure of the human TRPM4 channel subunit in complex with calcium and ATP at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.3 Å 44366 9b92 EMDB-44366, PDB-9b92: Cryo-EM structure of the human TRPM4 in complex with calcium at 18 degrees Celsius 手法: EM (単粒子) / 解像度: 3.5 Å 44367 9b93 EMDB-44367, PDB-9b93: Cryo-EM structure of the human TRPM4 channel in the presence of EDTA at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.1 Å 44368 9b94 EMDB-44368, PDB-9b94: Cryo-EM structure of the E396A mutant of human TRPM4 in complex with calcium at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 3.1 Å EMDB-44369: Cryo-EM structure of the human TRPM4 channel in complex with calcium, decavanadate and ATP at 37 degrees Celsius 手法: EM (単粒子) / 解像度: 4.4 Å
化合物	ChemComp-CA: Unknown entry / カルシウムジカチオン ChemComp-DVT: DECAVANADATE ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP / ATP, エネルギー貯蔵分子*YM
由来	homo sapiens (ヒト)
キーワード	TRANSPORT PROTEIN / ion channel / TRP channel / MEMBRANE PROTEIN