+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6jhn | ||||||
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タイトル | Structure of RyR2 (F/C/Ca2+ dataset) | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / cryo-EM (低温電子顕微鏡法) | ||||||
機能・相同性 | 機能・相同性情報 positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of insulin secretion involved in cellular response to glucose stimulus / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / cell communication by electrical coupling involved in cardiac conduction / response to redox state / protein maturation by protein folding / 'de novo' protein folding ...positive regulation of sequestering of calcium ion / cyclic nucleotide binding / negative regulation of release of sequestered calcium ion into cytosol / negative regulation of insulin secretion involved in cellular response to glucose stimulus / neuronal action potential propagation / insulin secretion involved in cellular response to glucose stimulus / cell communication by electrical coupling involved in cardiac conduction / response to redox state / protein maturation by protein folding / 'de novo' protein folding / negative regulation of heart rate / negative regulation of phosphoprotein phosphatase activity / FK506 binding / positive regulation of axon regeneration / : / smooth muscle contraction / negative regulation of ryanodine-sensitive calcium-release channel activity / response to vitamin E / calcium channel inhibitor activity / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / protein peptidyl-prolyl isomerization / T cell proliferation / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / release of sequestered calcium ion into cytosol / Ion homeostasis / regulation of ryanodine-sensitive calcium-release channel activity / sarcoplasmic reticulum membrane / calcium channel complex / regulation of cytosolic calcium ion concentration / プロリルイソメラーゼ / peptidyl-prolyl cis-trans isomerase activity / response to hydrogen peroxide / Stimuli-sensing channels / Z disc / positive regulation of cytosolic calcium ion concentration / protein refolding / transmembrane transporter binding / signaling receptor binding / 生体膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Sus scrofa (ブタ) | ||||||
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: 4.5 Å | ||||||
データ登録者 | Chi, X.M. / Gong, D.S. / Ren, K. / Zhou, G.W. / Huang, G.X.Y. / Lei, J.L. / Zhou, Q. / Yan, N. | ||||||
引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2019 タイトル: Molecular basis for allosteric regulation of the type 2 ryanodine receptor channel gating by key modulators. 著者: Ximin Chi / Deshun Gong / Kang Ren / Gewei Zhou / Gaoxingyu Huang / Jianlin Lei / Qiang Zhou / Nieng Yan / 要旨: The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron ...The type 2 ryanodine receptor (RyR2) is responsible for releasing Ca from the sarcoplasmic reticulum of cardiomyocytes, subsequently leading to muscle contraction. Here, we report 4 cryo-electron microscopy (cryo-EM) structures of porcine RyR2 bound to distinct modulators that, together with our published structures, provide mechanistic insight into RyR2 regulation. Ca alone induces a contraction of the central domain that facilitates the dilation of the S6 bundle but is insufficient to open the pore. The small-molecule agonist PCB95 helps Ca to overcome the barrier for opening. FKBP12.6 induces a relaxation of the central domain that decouples it from the S6 bundle, stabilizing RyR2 in a closed state even in the presence of Ca and PCB95. Although the channel is open when PCB95 is replaced by caffeine and adenosine 5'-triphosphate (ATP), neither of the modulators alone can sufficiently counter the antagonistic effect to open the channel. Our study marks an important step toward mechanistic understanding of the sophisticated regulation of this key channel whose aberrant activity engenders life-threatening cardiac disorders. | ||||||
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 | 6jhn.cif.gz | 2.4 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6jhn.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 6jhn.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/jh/6jhn ftp://data.pdbj.org/pub/pdb/validation_reports/jh/6jhn | HTTPS FTP |
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-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: 564905.625 Da / 分子数: 4 / 由来タイプ: 天然 / 由来: (天然) Sus scrofa (ブタ) #2: タンパク質 | 分子量: 11798.501 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: FKBP1B, FKBP12.6, FKBP1L, FKBP9, OTK4 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P68106, プロリルイソメラーゼ #3: 化合物 | ChemComp-ZN / #4: 化合物 | ChemComp-CA / #5: 化合物 | ChemComp-CFF / |
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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: RyR2 in complex with FKBP12.6Ryanodine receptor 2 / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: NATURAL |
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由来(天然) | 生物種: Sus scrofa (ブタ) |
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 FIELDBright-field microscopy |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
3次元再構成 | 解像度: 4.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 77339 / 対称性のタイプ: POINT |