Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

J Membr Biol

School of Biological Sciences, National Institute of Science Education and Research, An OCC of Homi Bhabha National Institute, Khordha, Jatni, Odisha, 752050, India.

Published: December 2024


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Article Abstract

TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584472PMC
http://dx.doi.org/10.1007/s00232-024-00319-yDOI Listing

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Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.

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TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues.

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