Thermosensitive TRP channel pore turret is part of the temperature activation pathway

Fan Yang, Yuanyuan Cui, KeWei Wang, Jie Zheng

Research output: Contribution to journalArticle

127 Scopus citations

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 activationand is not observed duringligand- 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.

Original languageEnglish (US)
Pages (from-to)7083-7088
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number15
DOIs
StatePublished - Apr 13 2010

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Keywords

  • Conformational change
  • Fluorescence resonance energy transfer
  • Temperature sensing
  • Thermodynamics

ASJC Scopus subject areas

  • General

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