ArticleResearch square2025
Ligand-induced cold activation of TRPV3.
Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Both hot and cold sensation of the homotetrameric thermosensitive transient receptor potential vanilloid 1-4 (TRPV1-4) channels have been predicted by a single Gibbs-Helmholtz equation for a change in molar heat capacity. However, cold activation has not been confirmed for those heat-responsive TRPV1-4 channels. Given the cooperative heat unfolding and non-cooperative cold unfolding behaviors in proteins, two different open states at low and high temperatures should be detected in TRPV1-4 channels. To test this hypothesis, the temperature-dependent quaternary and tertiary structures of oxidized TRPV3 in the presence and absence of the natural cannabinoid tetrahydrocannabivarin (THCV) were characterized along a lipid-dependent minimal gating pathway. Further thermoring analyses showed that gating state-dependent thermostability allowed oxidized TRPV3 to be activated and then inactivated only below 30°C. However, no inactivation would be observed above 30°C once the lipid at the active vanilloid site was released by THCV binding. Therefore, such two temperature-dependent gating pathways of oxidized TRPV3 actually resulted from cold and heat activation. (161 words).
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