8BDC

Human apo TRPM8 in a closed state (composite map)

8BDC の概要

• エントリーDOI: 10.2210/pdb8bdc/pdb
• EMDBエントリー: 15981 15982 15983
• 分子名称: Transient receptor potential cation channel subfamily M member 8, CHOLESTEROL HEMISUCCINATE, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, ... (5 entities in total)
• 機能のキーワード: calcium ion channel, cold temperature sensor, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 519362.14

構造登録者

Palchevskyi, S.,Czarnocki-Cieciura, M.,Vistoli, G.,Gervasoni, S.,Nowak, E.,Beccari, A.R.,Nowotny, M.,Talarico, C. (登録日: 2022-10-19, 公開日: 2023-11-01, 最終更新日: 2024-10-23)

主引用文献

Palchevskyi, S.,Czarnocki-Cieciura, M.,Vistoli, G.,Gervasoni, S.,Nowak, E.,Beccari, A.R.,Nowotny, M.,Talarico, C.
Structure of human TRPM8 channel.
Commun Biol, 6:1065-1065, 2023

PubMed Abstract: TRPM8 is a non-selective cation channel permeable to both monovalent and divalent cations that is activated by multiple factors, such as temperature, voltage, pressure, and changes in osmolality. It is a therapeutic target for anticancer drug development, and its modulators can be utilized for several pathological conditions. Here, we present a cryo-electron microscopy structure of a human TRPM8 channel in the closed state that was solved at 2.7 Å resolution. Our structure comprises the most complete model of the N-terminal pre-melastatin homology region. We also visualized several lipids that are bound by the protein and modeled how the human channel interacts with icilin. Analyses of pore helices in available TRPM structures showed that all these structures can be grouped into different closed, desensitized and open state conformations based on the register of the pore helix S6 which positions particular amino acid residues at the channel constriction.

PubMed: 37857704
DOI: 10.1038/s42003-023-05425-6

実験手法

ELECTRON MICROSCOPY (2.65 Å)