The next installment of the monthly methods-focused webinar series hosted by the National Center for CryoEM Access and Training (NCCAT), the Pacific Northwest Center for CryoEM (PNCC), and the Stanford-SLAC CryoEM Center (S2C2) will be held on
Thursday March 31, 2022 at 12 PM eastern / 9 AM pacific time
Dohoon Kwon, Ph.D., Post-Doctoral Scholar, Lee Laboratory, Duke University
Heat-dependent opening of TRPV1 in the presence of capsaicin
Talk Abstract: Transient receptor potential vanilloid member 1 (TRPV1) is a Ca2+-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. In published work, we determined the structures of apo and capsaicin-bound full-length rat TRPV1 reconstituted into lipid nanodiscs over a range of temperatures using cryo-EM. This has allowed us to visualize the noxious heat-induced opening of TRPV1 in the presence of capsaicin. Heat-dependent TRPV1 opening comprises stepwise conformational transitions. Global conformational changes across multiple subdomains of TRPV1 are followed by the rearrangement of the outer pore, leading to gate opening. Solvent-accessible surface area analyses and functional studies suggest that a subset of residues form an interaction network directly involved in heat sensing. Our study provides a glimpse of the molecular principles underlying noxious physical and chemical stimuli sensing by TRPV1, which can be extended to other thermal sensing ion channels. In this talk, I will also discuss how to prepare the grids at high-temperature conditions and the recent results we have obtained at various temperatures.