+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ymq | ||||||
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タイトル | OSCA1.1-F516A nanodisc | ||||||
要素 | Protein OSCA1 | ||||||
キーワード | MEMBRANE PROTEIN / OSCA1.1-F516A nanodisc | ||||||
機能・相同性 | 機能・相同性情報 regulation of calcium ion import / calcium-activated cation channel activity / cellular hyperosmotic response / response to osmotic stress / monoatomic cation channel activity / protein tetramerization / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Arabidopsis thaliana (シロイヌナズナ) | ||||||
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: 2.6 Å | ||||||
データ登録者 | Zhang, M.F. | ||||||
資金援助 | 1件
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引用 | ジャーナル: Nat Commun / 年: 2024 タイトル: Activation mechanisms of dimeric mechanosensitive OSCA/TMEM63 channels. 著者: Yuanyue Shan / Mengmeng Zhang / Meiyu Chen / Xinyi Guo / Ying Li / Mingfeng Zhang / Duanqing Pei / 要旨: OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation ...OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation mechanism of these transporter-like channels is not fully understood. Here we report cryo-EM structures of a dimeric OSCA/TMEM63 pore mutant OSCA1.1-F516A with a sequentially extracellular dilated pore in a detergent environment. These structures suggest that the extracellular pore sequential dilation resembles a flower blooming and couples to a sequential contraction of each monomer subunit towards the dimer interface and subsequent extrusion of the dimer interface lipids. Interestingly, while OSCA1.1-F516A remains non-conducting in the native lipid environment, it can be directly activated by lyso-phosphatidylcholine (Lyso-PC) with reduced single-channel conductance. Structural analysis of OSCA1.1-F516A in lyso-PC-free and lyso-PC-containing lipid nanodiscs indicates that lyso-PC induces intracellular pore dilation by attracting the M6b to upward movement away from the intracellular side thus extending the intracellular pore. Further functional studies indicate that full activation of MS OSCA/TMEM63 dimeric channels by high-threshold mechanical force also involves the opening of both intercellular and extracellular pores. Our results provide the fundamental activation paradigm of the unique transporter-like MS OSCA/TMEM63 channels, which is likely applicable to functional branches of the TMEM63/TMEM16/TMC superfamilies. #1: ジャーナル: Nat Commun / 年: 2024 タイトル: Activation mechanisms of dimeric mechanosensitive OSCA/TMEM63 channels. 著者: Yuanyue Shan / Mengmeng Zhang / Meiyu Chen / Xinyi Guo / Ying Li / Mingfeng Zhang / Duanqing Pei / 要旨: OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation ...OSCA/TMEM63 channels, which have transporter-like architectures, are bona fide mechanosensitive (MS) ion channels that sense high-threshold mechanical forces in eukaryotic cells. The activation mechanism of these transporter-like channels is not fully understood. Here we report cryo-EM structures of a dimeric OSCA/TMEM63 pore mutant OSCA1.1-F516A with a sequentially extracellular dilated pore in a detergent environment. These structures suggest that the extracellular pore sequential dilation resembles a flower blooming and couples to a sequential contraction of each monomer subunit towards the dimer interface and subsequent extrusion of the dimer interface lipids. Interestingly, while OSCA1.1-F516A remains non-conducting in the native lipid environment, it can be directly activated by lyso-phosphatidylcholine (Lyso-PC) with reduced single-channel conductance. Structural analysis of OSCA1.1-F516A in lyso-PC-free and lyso-PC-containing lipid nanodiscs indicates that lyso-PC induces intracellular pore dilation by attracting the M6b to upward movement away from the intracellular side thus extending the intracellular pore. Further functional studies indicate that full activation of MS OSCA/TMEM63 dimeric channels by high-threshold mechanical force also involves the opening of both intercellular and extracellular pores. Our results provide the fundamental activation paradigm of the unique transporter-like MS OSCA/TMEM63 channels, which is likely applicable to functional branches of the TMEM63/TMEM16/TMC superfamilies. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8ymq.cif.gz | 242 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8ymq.ent.gz | 192.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8ymq.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 | 8ymq_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8ymq_full_validation.pdf.gz | 1.6 MB | 表示 | |
XML形式データ | 8ymq_validation.xml.gz | 53 KB | 表示 | |
CIF形式データ | 8ymq_validation.cif.gz | 76 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ym/8ymq ftp://data.pdbj.org/pub/pdb/validation_reports/ym/8ymq | HTTPS FTP |
-関連構造データ
関連構造データ | 39403MC 8ymmC 8ymnC 8ymoC 8ympC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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: 87620.914 Da / 分子数: 2 / 変異: F516A / 由来タイプ: 組換発現 由来: (組換発現) Arabidopsis thaliana (シロイヌナズナ) 遺伝子: OSCA1, OSCA1.1, At4g04340, T19B17.6 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q9XEA1 #2: 化合物 | ChemComp-PEE / 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: OSCA1.1-F516A pre-open 1 / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Arabidopsis thaliana (シロイヌナズナ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
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 |
-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: 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 / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 2.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 60000 / 対称性のタイプ: POINT |