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TitleStructures of a mammalian TRPM8 in closed state.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 3113, Year 2022
Publish dateJun 3, 2022
AuthorsCheng Zhao / Yuan Xie / Lizhen Xu / Fan Ye / Ximing Xu / Wei Yang / Fan Yang / Jiangtao Guo /
PubMed AbstractTransient 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 ...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.
External linksNat Commun / PubMed:35662242 / PubMed Central
MethodsEM (single particle)
Resolution2.52 - 3.21 Å
Structure data

32720

7wra

EMDB-32720, PDB-7wra:
Mouse TRPM8 in LMNG in ligand-free state
Method: EM (single particle) / Resolution: 2.98 Å

32721

7wrb

EMDB-32721, PDB-7wrb:
Mouse TRPM8 in LMNG in the presence of calcium
Method: EM (single particle) / Resolution: 2.88 Å

32722

7wrc

EMDB-32722, PDB-7wrc:
Mouse TRPM8 in LMNG in the presence of calcium, icilin and PI(4,5)P2
Method: EM (single particle) / Resolution: 3.21 Å

32723

7wrd

EMDB-32723, PDB-7wrd:
Mouse TRPM8 in LMNG in the presence of calcium and icilin
Method: EM (single particle) / Resolution: 2.98 Å

32724

7wre

EMDB-32724, PDB-7wre:
Mouse TRPM8 in lipid nanodiscs in the presence of calcium and icilin
Method: EM (single particle) / Resolution: 2.52 Å

32725

7wrf

EMDB-32725, PDB-7wrf:
Mouse TRPM8 in lipid nanodiscs in the presence of calcium, icilin and PI(4,5)P2
Method: EM (single particle) / Resolution: 3.04 Å

Chemicals

ChemComp-NA:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-KX7:
Icilin / agonist*YM

Source
  • mus musculus (house mouse)
KeywordsTRANSPORT PROTEIN / TRPM8

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