Temperature Controlled Helix-Helix Interactions In Desk Minimal Sensor

DesK is a temperature sensing transmembrane protein that acts as a molecular switch to regulate membrane fluidity as a function of temperature change. The full function of DesK is modelled by a chimeric construct, denominated minimal sensor (MS), formed by the upper and lower halves of transmembrane helices 1 and 5, respectively. The signalling by MS has been explored experimentally providing data for modelling studies. Resulting from this, the current view is that it forms a dimer, switching its conformation depending on the temperature. To further investigate the molecular details of the switch mechanism, we have developed a new method for exploring the energy landscape of interaction, which allows high throughput screening of transmembrane helix dimers. The results show a clear distinction between helix-helix interactions at high and at low temperatures, providing a molecular basis for the functioning of the minimal sensor. These results form the basis for further experimental exploration, as well as for the rational design of other switching sensors.