| Popis: |
Physiological sensation of heat or cold in higher organisms is mediated by specialized ion channels whose opening and closing is exquisitely regulated by ambient temperatures. Members of TRP channel family, a branch of the much larger voltage-gated ion channel superfamily, serve as the primary physiological thermo-sensors. However, the physicochemical underpinnings of high temperature-sensitivity of channel gating remain poorly understood. Here, using a heuristic protein design approach, we have transmuted a temperature-insensitive potassium channel into a heat or a cold-sensitive channel. By varying amino acid polarities at sites undergoing state-dependent changes in solvation, we were able to systematically confer temperature-sensing phenotype to a prototypical voltage-dependent potassium channel. We also demonstrate that magnitude of voltage-sensing charges inversely modulate temperature-sensitivity consistent with predictions of thermodynamic coupling. These emerging molecular principles provide a template to understand varied temperature-dependent gating phenotype in channels with conserved transmembrane architecture. |
