タンパク質・ペプチド: Transient receptor potential cation channel, subfamily M, member 2
キーワード
TRANSPORT PROTEIN
機能・相同性
機能・相同性情報
TRP channels / Neutrophil degranulation / ADP-D-ribose binding / mono-ADP-D-ribose binding / ligand-gated calcium channel activity / ligand-gated monoatomic cation channel activity / monoatomic ion channel activity / calcium ion transmembrane transport / calcium channel activity / protein homotetramerization ...TRP channels / Neutrophil degranulation / ADP-D-ribose binding / mono-ADP-D-ribose binding / ligand-gated calcium channel activity / ligand-gated monoatomic cation channel activity / monoatomic ion channel activity / calcium ion transmembrane transport / calcium channel activity / protein homotetramerization / calcium ion binding / plasma membrane 類似検索 - 分子機能
TRPM, SLOG domain / : / SLOG in TRPM / TRPM2-like domain / NUDIX hydrolase-like domain superfamily / Ion transport domain / Ion transport protein 類似検索 - ドメイン・相同性
Transient receptor potential cation channel subfamily M member 2 / : 類似検索 - 構成要素
ジャーナル: Nature / 年: 2018 タイトル: Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium. 著者: Yihe Huang / Paige A Winkler / Weinan Sun / Wei Lü / Juan Du / 要旨: 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 ...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.