Transient receptor potential cation channel subfamily M member 2
キーワード
TRANSPORT PROTEIN / channel / trpm2 / Selectivity Filter
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 / dendritic cell chemotaxis / calcium ion transmembrane import into cytosol / temperature homeostasis / : / intracellularly gated calcium channel activity / calcium ion import across plasma membrane / tertiary granule membrane / ficolin-1-rich granule 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 Natural Science Foundation of China (NSFC)
31872796
中国
National Natural Science Foundation of China (NSFC)
81371302
中国
引用
ジャーナル: Cell Rep / 年: 2021 タイトル: Structural and functional basis of the selectivity filter as a gate in human TRPM2 channel. 著者: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan ...著者: Xiafei Yu / Yuan Xie / Xiaokang Zhang / Cheng Ma / Likun Liu / Wenxuan Zhen / Lingyi Xu / Jianmin Zhang / Yan Liang / Lixia Zhao / Xiuxia Gao / Peilin Yu / Jianhong Luo / Lin-Hua Jiang / Yan Nie / Fan Yang / Jiangtao Guo / Wei Yang / 要旨: Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is ...Transient receptor potential melastatin 2 (TRPM2), a Ca-permeable cation channel, is gated by intracellular adenosine diphosphate ribose (ADPR), Ca, warm temperature, and oxidative stress. It is critically involved in physiological and pathological processes ranging from inflammation to stroke to neurodegeneration. At present, the channel's gating and ion permeation mechanisms, such as the location and identity of the selectivity filter, remain ambiguous. Here, we report the cryo-electron microscopy (cryo-EM) structure of human TRPM2 in nanodisc in the ligand-free state. Cryo-EM map-guided computational modeling and patch-clamp recording further identify a quadruple-residue motif as the ion selectivity filter, which adopts a restrictive conformation in the closed state and acts as a gate, profoundly contrasting with its widely open conformation in the Nematostella vectensis TRPM2. Our study reveals the gating of human TRPM2 by the filter and demonstrates the feasibility of using cryo-EM in conjunction with computational modeling and functional studies to garner structural information for intrinsically dynamic but functionally important domains.
履歴
登録
2021年10月18日
登録サイト: PDBJ / 処理サイト: PDBJ
改定 1.0
2021年12月22日
Provider: repository / タイプ: Initial release
改定 1.1
2024年6月19日
Group: Data collection / カテゴリ: chem_comp_atom / chem_comp_bond
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