11 research outputs found
A Synaptic Vesicle-Associated Ca2+ Channel Promotes Endocytosis and Couples Exocytosis to Endocytosis
Functional and Structural Studies of TRP Channels Heterologously Expressed in Budding Yeast
Probing Structure and Function of Ion Channels Using Limited Proteolysis and Microfluidics
Understand spiciness: mechanism of TRPV1 channel activation by capsaicin
Abstract Capsaicin in chili peppers bestows the sensation of spiciness. Since the discovery of its receptor, transient receptor potential vanilloid 1 (TRPV1) ion channel, how capsaicin activates this channel has been under extensive investigation using a variety of experimental techniques including mutagenesis, patch-clamp recording, crystallography, cryo-electron microscopy, computational docking and molecular dynamic simulation. A framework of how capsaicin binds and activates TRPV1 has started to merge: capsaicin binds to a pocket formed by the channel’s transmembrane segments, where it takes a “tail-up, head-down” configuration. Binding is mediated by both hydrogen bonds and van der Waals interactions. Upon binding, capsaicin stabilizes the open state of TRPV1 by “pull-and-contact” with the S4-S5 linker. Understanding the ligand-host interaction will greatly facilitate pharmaceutical efforts to develop novel analgesics targeting TRPV1