title: Thermosensitive TRP channel pore turret is part of the temperature activation pathway.
abstract: Temperature sensing is crucial for homeotherms, including human beings, to maintain a stable body core temperature and respond to the ambient environment. A group of exquisitely temperature-sensitive transient receptor potential channels, termed thermoTRPs, serve as cellular temperature sensors. How thermoTRPs convert thermal energy (heat) into protein conformational changes leading to channel opening remains unknown. Here we demonstrate that the pathway for temperature-dependent activation is distinct from those for ligand- and voltage-dependent activation and involves the pore turret. We found that mutant channels with an artificial pore turret sequence lose temperature sensitivity but maintain normal ligand responses. Using site-directed fluorescence recordings we observed that temperature change induces a significant rearrangement of TRPV1 pore turret that is coupled to channel opening. This movement is specifically associated to temperature-dependent activation and is not observed during ligand- and voltage-dependent channel activation. These observations suggest that the turret is part of the temperature-sensing apparatus in thermoTRP channels, and its conformational change may give rise to the large entropy that defines high temperature sensitivity.
authors.affiliation: Department of Physiology and Membrane Biology, University of California Davis, Davis, CA 95616, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Cui
authors.forename: KeWei
authors.initials: K
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002460:Cell Line; D006358:Hot Temperature; D006801:Humans; D008024:Ligands; D008164:Luminescent Proteins / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D050052:TRPC Cation Channels / Q000737:chemistry / Q000502:physiology*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D008164:Luminescent Proteins; D050052:TRPC Cation Channels; C054562:yellow fluorescent protein, Bacteria