7WRF

Mouse TRPM8 in lipid nanodiscs in the presence of calcium, icilin and PI(4,5)P2

Summary for 7WRF

• Entry DOI: 10.2210/pdb7wrf/pdb
• EMDB information: 32725
• Descriptor: Transient receptor potential cation channel subfamily M member 8, CALCIUM ION, SODIUM ION, ... (4 entities in total)
• Functional Keywords: trpm8, transport protein
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 4
• Total formula weight: 519597.38

Authors

Zhao, C.,Xie, Y.,Guo, J. (deposition date: 2022-01-26, release date: 2022-06-22, Last modification date: 2024-10-16)

Primary citation

Zhao, C.,Xie, Y.,Xu, L.,Ye, F.,Xu, X.,Yang, W.,Yang, F.,Guo, J.
Structures of a mammalian TRPM8 in closed state.
Nat Commun, 13:3113-3113, 2022

PubMed Abstract: Transient receptor potential melastatin 8 (TRPM8) channel is a Ca-permeable non-selective cation channel that acts as the primary cold sensor in humans. TRPM8 is also activated by ligands such as menthol, icilin, and phosphatidylinositol 4,5-bisphosphate (PIP), and desensitized by Ca. Here we have determined electron cryo-microscopy structures of mouse TRPM8 in the absence of ligand, and in the presence of Ca and icilin at 2.5-3.2 Å resolution. The ligand-free state TRPM8 structure represents the full-length structure of mammalian TRPM8 channels with a canonical S4-S5 linker and the clearly resolved selectivity filter and outer pore loop. TRPM8 has a short but wide selectivity filter which may account for its permeability to hydrated Ca. Ca and icilin bind in the cytosolic-facing cavity of the voltage-sensing-like domain of TRPM8 but induce little conformational change. All the ligand-bound TRPM8 structures adopt the same closed conformation as the ligand-free structure. This study reveals the overall architecture of mouse TRPM8 and the structural basis for its ligand recognition.

PubMed: 35662242
DOI: 10.1038/s41467-022-30919-y

Experimental method

ELECTRON MICROSCOPY (3.04 Å)