2. Academic Validation
  3. Current View of Ligand and Lipid Recognition by the Menthol Receptor TRPM8

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

  • Trends Biochem Sci. 2020 Sep;45(9):806-819. doi: 10.1016/j.tibs.2020.05.008.
Ying Yin 1,  Seok-Yong Lee 2
Affiliations

Affiliations

  • 1 Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
  • 2 Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: [email protected].
PMID: 32532587 DOI: 10.1016/j.tibs.2020.05.008
Abstract

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.

Keywords

PI(4,5)P(2) regulation; allosteric coupling; cold receptor; cooling agent; menthol receptor; transient receptor potential ion channels.

Figures