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-Structure paper
タイトル | Structures of a mammalian TRPM8 in closed state. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 3113, Year 2022 |
掲載日 | 2022年6月3日 |
著者 | Cheng Zhao / Yuan Xie / Lizhen Xu / Fan Ye / Ximing Xu / Wei Yang / Fan Yang / Jiangtao Guo / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:35662242 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.52 - 3.21 Å |
構造データ | EMDB-32720, PDB-7wra: EMDB-32721, PDB-7wrb: EMDB-32722, PDB-7wrc: EMDB-32723, PDB-7wrd: EMDB-32724, PDB-7wre: EMDB-32725, PDB-7wrf: |
化合物 | ChemComp-NA: ChemComp-CA: ChemComp-KX7: |
由来 |
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キーワード | TRANSPORT PROTEIN / TRPM8 |