Thermoring basis for the TRPV3 bio-thermometer

Abstract

The thermosensitive transient receptor potential (TRP) channels are well-known as bio-thermometers with specific temperature thresholds and sensitivity. However, their precise 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 constrained thermo-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 the specific temperature thresholds to initiate channel gating while the smaller grids may be required to secure heat efficacy. Together, all the grids along the lipid-dependent minimal gating pathway may be necessary to change with molar heat capacity for the specific temperature sensitivity. Therefore, this graph theory-based grid thermodynamic model may provide an extensive structural basis for the thermo-gated TRP channels.