Alexander Sobolevsky, Associate Professor, Biochemistry & Molecular Biophysics, Columbia University Irving Medical Center, will give a talk on "Structural and functional studies of the temperature-sensitive TRP channel TRPV3"

ABSTRACT

Transient receptor potential (TRP) channels sense temperature in organisms ranging from yeast to human but the molecular mechanisms of thermosensation remain obscure. Here we present structures of the TRP channel TRPV3 in temperature-dependent open, closed and intermediate states that support a two-step model of its activation in response to heat. During the strongly temperature-dependent first step, sensitization, the channel pore remains closed while the S1-S4 and pore domains become more closely associated. The occupancies of lipid-binding sites surrounding these domains are reduced and S6 undergoes an a-to-p helical transition. During the weakly temperature-dependent second step, channel opening, the tight association of the S1-S4 and pore domains results in the complete extrusion of the lipids from their binding sites and splaying of the S6 helices. Together, these rearrangements are stabilized by structural changes in the linker domain and the C-terminus. Our results inform TRP channel temperature activation and highlight an important role in heat sensing by TRPV3 of its interactions with the surrounding membrane lipids.