title: A molecular framework for temperature-dependent gating of ion channels.
abstract: Perception of heat or cold in higher organisms is mediated by specialized ion channels whose gating is exquisitely sensitive to temperature. The physicochemical underpinnings of this temperature-sensitive gating have proven difficult to parse. Here, we took a bottom-up protein design approach and rationally engineered ion channels to activate in response to thermal stimuli. By varying amino acid polarities at sites undergoing state-dependent changes in solvation, we were able to systematically confer temperature sensitivity to a canonical voltage-gated ion channel. Our results imply that the specific heat capacity change during channel gating is a major determinant of thermosensitive gating. We also show that reduction of gating charges amplifies temperature sensitivity of designer channels, which accounts for low-voltage sensitivity in all known temperature-gated ion channels. These emerging principles suggest a plausible molecular mechanism for temperature-dependent gating that reconcile how ion channels with an overall conserved transmembrane architecture may exhibit a wide range of temperature-sensing phenotypes. :
authors.affiliation: Graduate Program in Biophysics, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA; Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA.
authors.forename: Sandipan
authors.initials: S
authors.lastname: Chowdhury
authors.affiliation: Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Jarecki
authors.affiliation: Graduate Program in Biophysics, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA; Department of Neuroscience, 1111 Highland Ave, School of Medicine and Public Health, University of Wisconsin, Madison, Madison, WI 53705, USA. Electronic address: chanda@wisc.edu.
authors.forename: Baron
authors.initials: B
authors.lastname: Chanda
mesh_terms: D000818:Animals; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D015202:Protein Engineering; D051381:Rats; D013696:Temperature; D013816:Thermodynamics
chemical_list: D007473:Ion Channels