title: Structure-Driven Pharmacology of Transient Receptor Potential Channel Vanilloid 1.
abstract: The transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor that mediates the flux of cations across the membrane in response to several stimuli, including heat, voltage, and ligands. The best known agonist of TRPV1 channels is capsaicin, the pungent component of "hot" chili peppers. In addition, peptides found in the venom of poisonous animals, along with the lipids phosphatidylinositol 4,5-biphosphate, lysophosphatidic acid, and cholesterol, bind to TRPV1 with high affinity to modulate channel gating. Here, we discuss the functional evidence regarding ligand-dependent activation of TRPV1 channels in light of structural data recently obtained by cryoelectron microscopy. This review focuses on the mechanistic insights into ligand binding and allosteric gating of TRPV1 channels and the relevance of accurate polymodal receptor biophysical characterization for drug design in novel pain therapies.
authors.affiliation: Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile (I.D.-F., R.L., F.G.-N.); Centro de Bioinformática y Biología Integrativa, Universidad Andrés Bello, Santiago, Chile (I.D.-F., J.C.-M., R.V.S., F.G.-N.); and Fraunhofer Chile Research, Santiago, Chile (I.D.-F.) ignacio.diaz@cinv.cl ramon.latorre@uv.cl.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Díaz-Franulic
authors.affiliation: Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile (I.D.-F., R.L., F.G.-N.); Centro de Bioinformática y Biología Integrativa, Universidad Andrés Bello, Santiago, Chile (I.D.-F., J.C.-M., R.V.S., F.G.-N.); and Fraunhofer Chile Research, Santiago, Chile (I.D.-F.).
authors.forename: Javier
authors.initials: J
authors.lastname: Caceres-Molina
authors.affiliation: Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile (I.D.-F., R.L., F.G.-N.); Centro de Bioinformática y Biología Integrativa, Universidad Andrés Bello, Santiago, Chile (I.D.-F., J.C.-M., R.V.S., F.G.-N.); and Fraunhofer Chile Research, Santiago, Chile (I.D.-F.).
authors.forename: Romina V
authors.initials: RV
authors.lastname: Sepulveda
authors.affiliation: Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile (I.D.-F., R.L., F.G.-N.); Centro de Bioinformática y Biología Integrativa, Universidad Andrés Bello, Santiago, Chile (I.D.-F., J.C.-M., R.V.S., F.G.-N.); and Fraunhofer Chile Research, Santiago, Chile (I.D.-F.).
authors.forename: Fernando
authors.initials: F
authors.lastname: Gonzalez-Nilo
authors.affiliation: Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile (I.D.-F., R.L., F.G.-N.); Centro de Bioinformática y Biología Integrativa, Universidad Andrés Bello, Santiago, Chile (I.D.-F., J.C.-M., R.V.S., F.G.-N.); and Fraunhofer Chile Research, Santiago, Chile (I.D.-F.) ignacio.diaz@cinv.cl ramon.latorre@uv.cl.
authors.forename: Ramon
authors.initials: R
authors.lastname: Latorre
mesh_terms: D000818:Animals; D001665:Binding Sites; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D008024:Ligands; D008055:Lipids / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D008024:Ligands; D008055:Lipids; D050916:TRPV Cation Channels