+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6v9x | |||||||||
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タイトル | Structure of TRPA1 modified by iodoacetamide, PMAL-C8 | |||||||||
要素 | Transient receptor potential cation channel subfamily A member 1 | |||||||||
キーワード | TRANSPORT PROTEIN / Transient receptor potential cation channel subfamily A member 1 / membrane protein | |||||||||
機能・相同性 | 機能・相同性情報 temperature-gated cation channel activity / stereocilium bundle / detection of chemical stimulus involved in sensory perception of pain / thermoception / TRP channels / channel activity / response to pain / : / intracellularly gated calcium channel activity / detection of mechanical stimulus involved in sensory perception of pain ...temperature-gated cation channel activity / stereocilium bundle / detection of chemical stimulus involved in sensory perception of pain / thermoception / TRP channels / channel activity / response to pain / : / intracellularly gated calcium channel activity / detection of mechanical stimulus involved in sensory perception of pain / monoatomic ion transport / sensory perception of pain / response to cold / : / calcium ion transmembrane transport / calcium channel activity / response to organic cyclic compound / intracellular calcium ion homeostasis / cellular response to hydrogen peroxide / protein homotetramerization / cell surface receptor signaling pathway / response to xenobiotic stimulus / identical protein binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
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: 3.3 Å | |||||||||
データ登録者 | Zhao, J. / Lin King, J.V. / Paulsen, C.E. / Cheng, Y. / Julius, D. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nature / 年: 2020 タイトル: Irritant-evoked activation and calcium modulation of the TRPA1 receptor. 著者: Jianhua Zhao / John V Lin King / Candice E Paulsen / Yifan Cheng / David Julius / 要旨: The transient receptor potential ion channel TRPA1 is expressed by primary afferent nerve fibres, in which it functions as a low-threshold sensor for structurally diverse electrophilic irritants, ...The transient receptor potential ion channel TRPA1 is expressed by primary afferent nerve fibres, in which it functions as a low-threshold sensor for structurally diverse electrophilic irritants, including small volatile environmental toxicants and endogenous algogenic lipids. TRPA1 is also a 'receptor-operated' channel whose activation downstream of metabotropic receptors elicits inflammatory pain or itch, making it an attractive target for novel analgesic therapies. However, the mechanisms by which TRPA1 recognizes and responds to electrophiles or cytoplasmic second messengers remain unknown. Here we use strutural studies and electrophysiology to show that electrophiles act through a two-step process in which modification of a highly reactive cysteine residue (C621) promotes reorientation of a cytoplasmic loop to enhance nucleophilicity and modification of a nearby cysteine (C665), thereby stabilizing the loop in an activating configuration. These actions modulate two restrictions controlling ion permeation, including widening of the selectivity filter to enhance calcium permeability and opening of a canonical gate at the cytoplasmic end of the pore. We propose a model to explain functional coupling between electrophile action and these control points. We also characterize a calcium-binding pocket that is highly conserved across TRP channel subtypes and accounts for all aspects of calcium-dependent TRPA1 regulation, including potentiation, desensitization and activation by metabotropic receptors. These findings provide a structural framework for understanding how a broad-spectrum irritant receptor is controlled by endogenous and exogenous agents that elicit or exacerbate pain and itch. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6v9x.cif.gz | 434.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6v9x.ent.gz | 340.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6v9x.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 6v9x_validation.pdf.gz | 1007.8 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6v9x_full_validation.pdf.gz | 1020.5 KB | 表示 | |
XML形式データ | 6v9x_validation.xml.gz | 64.4 KB | 表示 | |
CIF形式データ | 6v9x_validation.cif.gz | 102.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/v9/6v9x ftp://data.pdbj.org/pub/pdb/validation_reports/v9/6v9x | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 127703.586 Da / 分子数: 4 / 変異: D966E / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TRPA1, ANKTM1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O75762 研究の焦点であるリガンドがあるか | 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 |
-試料調製
構成要素 | 名称: TRPA1 modified by iodoacetamide, solubilized in PMAL-C8 タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.4 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 株: HEK293F |
緩衝液 | pH: 8 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: unspecified |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI POLARA 300 |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 40 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 190112 / 対称性のタイプ: POINT |