- PDB-6puu: Human TRPM2 bound to 8-Br-cADPR and calcium -
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基本情報
登録情報
データベース: PDB / ID: 6puu
タイトル
Human TRPM2 bound to 8-Br-cADPR and calcium
要素
Transient receptor potential cation channel subfamily M member 2
キーワード
TRANSPORT PROTEIN (運搬体タンパク質) / TRPM2 channel / 8-Br-cADPR / calcium (カルシウム)
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 / response to purine-containing compound / ligand-gated calcium channel activity / dendritic cell differentiation / cellular response to temperature stimulus / regulation of filopodium assembly / sodium channel activity ...cellular response to purine-containing compound / mono-ADP-D-ribose binding / manganese ion transmembrane transporter activity / zinc ion transmembrane transport / response to purine-containing compound / ligand-gated calcium channel activity / dendritic cell differentiation / cellular response to temperature stimulus / regulation of filopodium assembly / sodium channel activity / calcium ion transmembrane import into cytosol / TRPチャネル / regulation of actin cytoskeleton reorganization / 発情周期 / response to hydroperoxide / dendritic cell chemotaxis / positive regulation of oxidative stress-induced neuron death / calcium-release channel activity / temperature homeostasis / cation transmembrane transport / calcium ion import across plasma membrane / ficolin-1-rich granule membrane / calcium-mediated signaling using intracellular calcium source / tertiary granule membrane / positive regulation of insulin secretion / release of sequestered calcium ion into cytosol / specific granule membrane / cation channel activity / cellular response to calcium ion / calcium ion transmembrane transport / calcium channel activity / calcium ion transport / cytoplasmic vesicle membrane / cellular response to hydrogen peroxide / perikaryon / response to heat / protein homotetramerization / lysosomal membrane / リソソーム / neuron projection / Neutrophil degranulation / calcium ion binding / integral component of plasma membrane / 細胞膜 類似検索 - 分子機能
Transient receptor potential cation channel subfamily M member 2 / SLOG in TRPM / TRPM, SLOG domain / Nudix hydrolase domain profile. / NUDIX hydrolase domain / NUDIX hydrolase-like domain superfamily / Ion transport protein / Ion transport domain 類似検索 - ドメイン・相同性
Chem-CV1 / 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.