Despite the fact that we have number of high-resolution structures of ion channels that are temperature-sensitive, the biophysical basis of temperature dependent gating has been confounding. Mutagenesis studies have implicated a number of sites dispersed throughout the protein structure as putative elements of the temperature-sensing machinery. Using a protein engineering approach, we were able to design a series of temperature-sensing ion channels by taking into account the heat capacity changes that accompany solvation and desolvation of side chains during channel gating. Our findings, for the first time, provide a plausible molecular mechanism but perhaps more importantly, demonstrate that a specialized temperature-sensing domain is not required to confer high temperature-sensitivity.
- Chowdhury S, Jarecki BW, Chanda B. A molecular framework for temperature-dependent gating of ion channels. Cell. 2014 Aug 28;158(5):1148-58. PubMed PMID: 25156949; PubMed Central PMCID: PMC4405168.
Check out the commentary by Chris Miller (Cell (2014) Pgs:977-979).
Video abstract by Baron Chanda