6DRK

Structure of TRPM2 ion channel receptor by single particle electron cryo-microscopy, Apo state

6DRK の概要

• エントリーDOI: 10.2210/pdb6drk/pdb
• EMDBエントリー: 7999 8901
• 分子名称: Transient receptor potential cation channel, subfamily M, member 2 (1 entity in total)
• 機能のキーワード: transport protein
• 由来する生物種: Danio rerio (Zebrafish)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 674923.19

構造登録者

Du, J.,Lu, W.,Huang, Y.,Winkler, P.,Sun, W. (登録日: 2018-06-12, 公開日: 2018-09-19, 最終更新日: 2025-05-14)

主引用文献

Huang, Y.,Winkler, P.A.,Sun, W.,Lu, W.,Du, J.
Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium.
Nature, 562:145-149, 2018

PubMed Abstract: Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis. TRPM2 is polymodal and can be activated by a wide range of stimuli, including temperature, oxidative stress and NAD-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca entry across the plasma membrane and Ca release from lysosomes, and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease. Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions.

PubMed: 30250252
DOI: 10.1038/s41586-018-0558-4

実験手法

ELECTRON MICROSCOPY (3.8 Å)