Abstract

The Transient Receptor Potential (TRP) ion channel is a large and functionally diverse superfamily, second only to the potassium channels. Members of TRP channel superfamily include the capsaicin receptor, TRPV1 , and the “wasabi” receptor, TRPA1 . TRPV1 is a polymodal signal detector that resides on primary afferent sensory neurons. It is a heat-activated cation channel that is also modulated by various inflammatory agents and contributes to acute and persistent pain. TRPA1 activation is triggered by various pungent agonists such as allyl-isothiocyanate from mustard and allicin from garlic, both generating pungent taste. Enabled by recent technological breakthroughs in single particle cryo-EM, we determined the atomic structures of both TRPV1 and TRPA1 . We also utilized their rich pharmacological information for structural investigation of these two channels in various functional states, aiming to elucidate the mechanism of channel activations.