Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Physiological temperature drives TRPM4 ligand recognition and gating.
Journal, issue, pages	Nature, Year 2024
Publish date	May 15, 2024
Authors	Jinhong Hu / Sung Jin Park / Tyler Walter / Ian J Orozco / Garrett O'Dea / Xinyu Ye / Juan Du / Wei Lü /
PubMed Abstract	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.
External links	Nature / PubMed:38750366
Methods	EM (single particle)
Resolution	3.0 - 3.5 Å
Structure data	44360 9b8w EMDB-44360, PDB-9b8w: Cryo-EM structure of the human TRPM4 in complex with calcium at 37 degrees Celsius Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.3 Å 44366 9b92 EMDB-44366, PDB-9b92: Cryo-EM structure of the human TRPM4 in complex with calcium at 18 degrees Celsius Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 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 Method: EM (single particle) / Resolution: 3.1 Å
Chemicals	ChemComp-CA: Unknown entry ChemComp-DVT: DECAVANADATE / Sodium decavanadate ChemComp-ATP: ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / ion channel / TRP channel / MEMBRANE PROTEIN