8E4P

Mouse TRPM8 structure determined in the ligand- and PI(4,5)P2-free condition, Class I , C0 state

8E4P の概要

• エントリーDOI: 10.2210/pdb8e4p/pdb
• EMDBエントリー: 27895
• 分子名称: Transient receptor potential cation channel subfamily M member 8, CHOLESTEROL HEMISUCCINATE (2 entities in total)
• 機能のキーワード: trpm8, menthol receptor, cold receptor, cold sensor, pi(4, 5)p2, cooling agonists, temperature sensing, ion channel, sensory transduction, transient receptor potential ion channel, membrane protein
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 532033.96

構造登録者

Yin, Y.,Zhang, F.,Feng, S.,Butay, K.J.,Borgnia, M.J.,Im, W.,Lee, S.-Y. (登録日: 2022-08-18, 公開日: 2022-10-26, 最終更新日: 2024-06-12)

主引用文献

Yin, Y.,Zhang, F.,Feng, S.,Butay, K.J.,Borgnia, M.J.,Im, W.,Lee, S.Y.
Activation mechanism of the mouse cold-sensing TRPM8 channel by cooling agonist and PIP 2.
Science, 378:eadd1268-eadd1268, 2022

PubMed Abstract: The transient receptor potential melastatin 8 (TRPM8) channel is the primary molecular transducer responsible for the cool sensation elicited by menthol and cold in mammals. TRPM8 activation is controlled by cooling compounds together with the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP). Our knowledge of cold sensation and the therapeutic potential of TRPM8 for neuroinflammatory diseases and pain will be enhanced by understanding the structural basis of cooling agonist- and PIP-dependent TRPM8 activation. We present cryo-electron microscopy structures of mouse TRPM8 in closed, intermediate, and open states along the ligand- and PIP-dependent gating pathway. Our results uncover two discrete agonist sites, state-dependent rearrangements in the gate positions, and a disordered-to-ordered transition of the gate-forming S6-elucidating the molecular basis of chemically induced cool sensation in mammals.

PubMed: 36227998
DOI: 10.1126/science.add1268

実験手法

ELECTRON MICROSCOPY (3.59 Å)