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Thermoring-based heat activation switches in the TRPV1 biothermometer.
Wang, Guangyu.
Afiliación
  • Wang G; Department of Physiology and Membrane Biology, University of California School of Medicine, Davis, CA 95616, USA; Department of Drug Research and Development, Institute of Biophysical Medico-chemistry, Reno, NV 89523, USA. Electronic address: gary.wang10@gmail.com.
Int J Biol Macromol ; 248: 125915, 2023 Sep 01.
Article en En | MEDLINE | ID: mdl-37481175
Non-covalent interactions in bio-macromolecules are individually weak but collectively important. How they take a concerted action in a complex biochemical reaction network to realize their thermal stability and activity is still challenging to study. Here graph theory was used to investigate how the temperature-dependent non-covalent interactions as identified in the 3D structures of the thermo-gated capsaicin receptor TRPV1 could form a systemic fluidic grid-like mesh network with topological grids constrained as the thermo-rings to govern heat-sensing. The results showed that the heat-evoked melting of the biggest grid initiated a matched temperature threshold to release the lipid from the active vanilloid site for channel activation. Meanwhile, smaller grids were required to stabilize heat efficacy. Altogether, the change in the total grid sizes upon the change in the total noncovalent interactions along the lipid-dependent gating pathway was necessary for the matched temperature sensitivity. Therefore, this grid thermodynamic model may be broadly significant for the structural thermostability and the functional thermoactivity of bio-macromolecules.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Capsaicina / Calor Idioma: En Revista: Int J Biol Macromol Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Capsaicina / Calor Idioma: En Revista: Int J Biol Macromol Año: 2023 Tipo del documento: Article Pais de publicación: Países Bajos