The 2021 Nobel Prize in Physiology was awarded to David Julius and Ardem Patapoutian for their pioneering work on the receptors of the somatosensory system, including transient receptor potential (TRP) ion channels. This talk will focus on my work with David Julius to understand the molecular mechanisms of how environmental and noxious stimuli activate the TRPA1 wasabi receptor. Using a combination of cryogenic electron microscopy and patch lamp electrophysiology, we deciphered a two-step mechanism of TRPA1 activation involving the modification of critical cysteines. This work helps to explain how TRPA1 is able to respond to a variety of chemical stimuli.
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