Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.
The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation. In this review we first discuss the allosteric coupling between the temperature and voltage sensor modules and the pore domain, and then discuss the thermodynamic foundations of thermo-TRP channel activation. We provide a structural overview of the molecular determinants of temperature sensing. We also posit an anisotropic thermal diffusion model that may explain the large temperature sensitivity of TRP channels. Additionally, we examine the effect of several ligands on TRP channel function and the evidence regarding their mechanisms of action.
Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago 8370146, Chile.|Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2366103, Chile; email: ignacio.diaz@cinv.cl , ramon.latorre@uv.cl.|Fraunhofer Chile Research, Las Condes 7550296, Santiago, Chile.
Ignacio
I
Diaz-Franulic
Institute of Computational Comparative Medicine, Nanotechnology Innovation Center of Kansas State, Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802.
Horacio
H
Poblete
Center for Bioinformatics and Integrative Biology, Facultad de Ciencias Biológicas, Universidad Andres Bello, Santiago 8370146, Chile.|Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2366103, Chile; email: ignacio.diaz@cinv.cl , ramon.latorre@uv.cl.
Germán
G
Miño-Galaz
Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2366103, Chile; email: ignacio.diaz@cinv.cl , ramon.latorre@uv.cl.
Carlos
C
González
Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2366103, Chile; email: ignacio.diaz@cinv.cl , ramon.latorre@uv.cl.
Ramón
R
Latorre
D000494:Allosteric Regulation; D000818:Animals; D006801:Humans; D015640:Ion Channel Gating; D008024:Ligands; D011485:Protein Binding; D013696:Temperature; D013816:Thermodynamics; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D050051:Transient Receptor Potential Channels
gating models; heat activation pathways; ligand binding; phosphatidylinositol 4,5-bisphosphate; temperature sensor; thermodynamics