A folding reaction at the C-terminal domain drives temperature sensing in TRPM8 channels.

ABSTRACT: In mammals, temperature-sensitive TRP channels make membrane conductance of cells extremely temperature dependent, allowing the detection of temperature ranging from noxious cold to noxious heat. We progressively deleted the distal carboxyl terminus domain (CTD) of the cold-activated melastatin receptor channel, TRPM8. We found that the enthalpy change associated with channel gating is proportional to the length of the CTD. Deletion of the last 36 amino acids of the CTD transforms TRPM8 into a reduced temperature-sensitivity channel (Q₁₀ ∼4). Exposing the intracellular domain to a denaturing agent increases the energy required to open the channel indicating that cold drives channel gating by stabilizing the folded state of the CTD. Experiments in the presence of an osmoticant ag

SUBMITTER: Diaz-Franulic I 

PROVIDER: S-EPMC7443914 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature