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基本情報
登録情報 | データベース: PDB / ID: 6drk | ||||||||||||||||||||||||||||||||||||||||||
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タイトル | Structure of TRPM2 ion channel receptor by single particle electron cryo-microscopy, Apo state | ||||||||||||||||||||||||||||||||||||||||||
![]() | Transient receptor potential cation channel, subfamily M, member 2 | ||||||||||||||||||||||||||||||||||||||||||
![]() | TRANSPORT PROTEIN | ||||||||||||||||||||||||||||||||||||||||||
機能・相同性 | ![]() 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 | ||||||||||||||||||||||||||||||||||||||||||
生物種 | ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.8 Å | ||||||||||||||||||||||||||||||||||||||||||
![]() | Du, J. / Lu, W. / Huang, Y. / Winkler, P. / Sun, W. | ||||||||||||||||||||||||||||||||||||||||||
![]() | ![]() 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. | ||||||||||||||||||||||||||||||||||||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 801.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 613.9 KB | 表示 | ![]() |
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アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 168730.797 Da / 分子数: 4 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: trpm2 / 細胞株 (発現宿主): HEK293 GnTI- / 発現宿主: ![]() Has protein modification | Y | |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: Ion channel 1 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.5 MDa / 実験値: YES |
由来(天然) | 生物種: ![]() ![]() |
由来(組換発現) | 生物種: Mammalia (両生類) |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 45 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: dev_3084: / 分類: 精密化 |
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EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 |
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
3次元再構成 | 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 183041 / 対称性のタイプ: POINT |