Thermoring basis for the TRPV3 bio-thermometer

The thermosensitive transient receptor potential (TRP) channels are well-known as bio-thermometers with specific temperature thresholds and sensitivity. However, their structural origins are still mysterious. Here, graph theory was used to test how the temperature-dependent non-covalent interactions as identified in the 3D structures of thermo-gated TRPV3 could form a systematic fluidic grid-like mesh network with the thermal rings from the biggest grids to the smallest ones as necessary structural motifs for the variable temperature thresholds and sensitivity. The results showed that the heat-evoked melting of the biggest grids may control temperature thresholds to activate the channel while the smaller grids may act as thermo-stable anchors to secure the channel activity. Together, all the grids along the gating pathway may be necessary for the specific temperature sensitivity. Therefore, this grid thermodynamic model may provide an extensive structural basis for the thermo-gated TRP channels.