Transient receptor potential cation channel subfamily M member 2
キーワード
TRANSPORT PROTEIN / TRPM2 channel / apo state
機能・相同性
機能・相同性情報
cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / sodium channel activity ...cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / dendritic cell differentiation / response to purine-containing compound / ligand-gated calcium channel activity / regulation of filopodium assembly / cellular response to temperature stimulus / sodium channel activity / TRP channels / response to hydroperoxide / calcium ion transmembrane import into cytosol / dendritic cell chemotaxis / temperature homeostasis / intracellularly gated calcium channel activity / tertiary granule membrane / : / ficolin-1-rich granule membrane / calcium ion import across plasma membrane / monoatomic cation channel activity / specific granule membrane / release of sequestered calcium ion into cytosol / cellular response to calcium ion / cell projection / regulation of actin cytoskeleton organization / calcium ion transmembrane transport / calcium channel activity / cytoplasmic vesicle membrane / cellular response to hydrogen peroxide / calcium ion transport / response to heat / perikaryon / protein homotetramerization / lysosome / lysosomal membrane / calcium ion binding / Neutrophil degranulation / plasma membrane 類似検索 - 分子機能
TRPM, SLOG domain / SLOG in TRPM / Nudix hydrolase domain profile. / NUDIX hydrolase 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
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS111031
米国
引用
ジャーナル: Elife / 年: 2019 タイトル: Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel. 著者: Yihe Huang / Becca Roth / Wei Lü / Juan Du / 要旨: TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca and ADP ribose (ADPR), an NAD-metabolite ...TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca and ADP ribose (ADPR), an NAD-metabolite produced under oxidative stress and neurodegenerative conditions, suggests a role in neurological disorders. We provide a central concept between triple-site ligand binding and the channel gating of human TRPM2. We show consecutive structural rearrangements and channel activation of TRPM2 induced by binding of ADPR in two indispensable locations, and the binding of Ca in the transmembrane domain. The 8-Br-cADPR-an antagonist of cADPR-binds only to the MHR1/2 domain and inhibits TRPM2 by stabilizing the channel in an apo-like conformation. We conclude that MHR1/2 acts as a orthostatic ligand-binding site for TRPM2. The NUDT9-H domain binds to a second ADPR to assist channel activation in vertebrates, but not necessary in invertebrates. Our work provides insights into the gating mechanism of human TRPM2 and its pharmacology.
A: Transient receptor potential cation channel subfamily M member 2 B: Transient receptor potential cation channel subfamily M member 2 C: Transient receptor potential cation channel subfamily M member 2 D: Transient receptor potential cation channel subfamily M member 2