Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8.

Journal Article (Journal Article;Review)

Transient receptor potential (TRP) melastatin member 8 (TRPM8), which is a calcium-permeable ion channel, functions as the primary molecular sensor of cold and menthol in humans. Recent cryoelectron microscopy (cryo-EM) studies of TRPM8 have shown distinct structural features in its architecture and domain assembly compared with the capsaicin receptor TRP vanilloid member 1 (TRPV1). Moreover, ligand-bound TRPM8 structures have uncovered unforeseen binding sites for both cooling agonists and membrane lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. These complex structures unveil the molecular basis of cooling agonist sensing by TRPM8 and the allosteric role of PI(4,5)P2 in agonist binding for TRPM8 activation. Here, we review the recent advances in TRPM8 structural biology and investigate the molecular principles governing the distinguishing role of TRPM8 as the evolutionarily conserved menthol receptor.

Full Text

Duke Authors

Cited Authors

  • Yin, Y; Lee, S-Y

Published Date

  • September 2020

Published In

Volume / Issue

  • 45 / 9

Start / End Page

  • 806 - 819

PubMed ID

  • 32532587

International Standard Serial Number (ISSN)

  • 0968-0004

Digital Object Identifier (DOI)

  • 10.1016/j.tibs.2020.05.008

Language

  • eng

Conference Location

  • England