Chicago - 4:00 PM - 5:00 PM
The Department of Pharmacology is pleased to welcome Dr. Kenton Swartz,Ph.D, Senior Investigator, Basic Neuroscience Program, NINDS, NIH
The following, is an overview of this seminar, as described by Dr. Swartz:
Protein toxins from venomous organisms have been valuable tools for investigating the structure and gating mechanisms of voltage-activated ion channels. Transient Receptor Potential (TRP) channels are a large family of ion channels that are activated by diverse stimuli and ligands, including second messengers, temperature, voltage and natural products such as capsaicin, menthol and wasabi. We have begun to investigate the structure and gating mechanisms of the heat-activated TRPV1 channel using the double-knot toxin (DkTx) from tarantula venom. I will present the structure of DkTx that we solved using NMR, and show how we have docked DkTx into the electron density maps from the recent single particle EM structure of the toxin bound TRPV1 channel to reveal a range of interesting features of the toxin-channel interaction. In particular, our results reveal that DkTx binds to the perimeter of the external pore of TRPV1 at the interface of the channel with the surrounding lipid membrane. I will also talk about functional experiments suggesting that DkTx and extracellular ions profoundly alter activation of TRPV1 by heat, implicating the external pore in the mechanism of temperature-sensing.