| Title | Thermosensitive TRP channel pore turret is part of the temperature activation pathway |
| Authors | Yang, Fan Cui, Yuanyuan Wang, KeWei Zheng, Jie |
| Affiliation | Univ Calif Davis, Dept Physiol & Membrane Biol, Davis, CA 95616 USA. Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Dept Neurobiol, Beijing 100083, Peoples R China. |
| Keywords | conformational change fluorescence resonance energy transfer temperature sensing thermodynamics NUCLEOTIDE-GATED CHANNELS VANILLOID RECEPTOR-I ION CHANNELS K+ CHANNEL POTASSIUM CHANNELS CRYSTAL-STRUCTURE HEAT ACTIVATION MOLECULAR-BASIS COLD RECEPTOR PATCH-CLAMP |
| Issue Date | 2010 |
| Publisher | proceedings of the national academy of sciences of the united states of america |
| Citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2010,107,(15),7083-7088. |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/395773 |
| ISSN | 0027-8424 |
| DOI | 10.1073/pnas.1000357107 |
| Indexed | SCI(E) |
| Appears in Collections: | 医学部待认领 |
