Thanks for the kind words!

6. Our work also raises interesting questions about whether endogenous TRPA1 modifications can perturb the TRPA1:calmodulin interaction to influence channel regulation. So many exciting questions to ask!

5. Together, our work suggests that calmodulin pre-associates with TRPA1 in cells to facilitate proper calcium regulation. Perhaps calmodulin is a TRPA1 auxiliary subunit?

4. Using a combination of biochemical, biophysical, and structural approaches, we characterized the TRPA1 DCTCaMBE:calmodulin interaction and found that it is driven exclusively by the calmodulin C-lobe with tightest binding observed at basal calcium concentration.

3. This effect could be partially rescued by increasing the extracellular calcium concentration, suggesting that calmodulin binding to the DCTCaMBE is part of a multi-step long-range allosteric mechanism to control TRPA1 inactivation.

2. We identified a highly conserved calmodulin binding site in the TRPA1 distal, structurally unresolved, cytoplasmic C-terminus (the DCTCaMBE). Genetic or biochemical ablation of calmodulin binding to this site slowed TRPA1 calcium inactivation 10-to-20 fold.

1. Calcium regulation is the primary TRPA1 regulatory mechanism that keeps its activity in check to sustain acute pain signaling and prevent aberrant signaling. This regulation is biphasic with initial channel potentiation followed by inactivation/desensitization. Mechanism has been unclear.