Work

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

Year: 2024

Type: 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.

Source: The Journal of Membrane Biology

DOI: 10.1007/s00232-024-00319-y

Authors: Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami

Institutions: National Institute of Science Education and Research, Homi Bhabha National Institute

Language: English

Topic: Ion Channels and Receptors

Subfield: Sensory Systems

Field: Neuroscience

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,590

Funder: National Institute of Science Education and Research