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基本情報
登録情報 | データベース: PDB / ID: 8vk4 | ||||||
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タイトル | Structure of mouse RyR1 in complex with S100A1 (high-Ca2+/CFF/ATP dataset) | ||||||
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![]() | MEMBRANE PROTEIN / Calcium / Ion Channel | ||||||
機能・相同性 | ![]() junctional membrane complex / TGF-beta receptor signaling activates SMADs / Calcineurin activates NFAT / mTORC1-mediated signalling / regulation of response to osmotic stress / cytoplasmic side of membrane / regulation of muscle contraction / sarcoplasmic reticulum calcium ion transport / transforming growth factor beta receptor binding / Stimuli-sensing channels ...junctional membrane complex / TGF-beta receptor signaling activates SMADs / Calcineurin activates NFAT / mTORC1-mediated signalling / regulation of response to osmotic stress / cytoplasmic side of membrane / regulation of muscle contraction / sarcoplasmic reticulum calcium ion transport / transforming growth factor beta receptor binding / Stimuli-sensing channels / type I transforming growth factor beta receptor binding / Ion homeostasis / heart trabecula formation / terminal cisterna / ryanodine receptor complex / ryanodine-sensitive calcium-release channel activity / S100 protein binding / release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / response to caffeine / ossification involved in bone maturation / ventricular cardiac muscle tissue morphogenesis / skin development / cellular response to ATP / regulation of heart contraction / organelle membrane / FK506 binding / cellular response to caffeine / positive regulation of sprouting angiogenesis / outflow tract morphogenesis / extrinsic component of cytoplasmic side of plasma membrane / regulation of ryanodine-sensitive calcium-release channel activity / smooth endoplasmic reticulum / voltage-gated calcium channel activity / skeletal muscle fiber development / striated muscle contraction / heart morphogenesis / muscle contraction / T cell proliferation / axon terminus / release of sequestered calcium ion into cytosol / regulation of cytosolic calcium ion concentration / sarcoplasmic reticulum membrane / calcium channel complex / T-tubule / Hsp70 protein binding / cellular response to calcium ion / sarcomere / negative regulation of transforming growth factor beta receptor signaling pathway / sarcoplasmic reticulum / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / calcium channel activity / cytoplasmic side of plasma membrane / sarcolemma / Z disc / cytokine-mediated signaling pathway / calcium ion transport / ATPase binding / protease binding / protein homotetramerization / vesicle / transmembrane transporter binding / calmodulin binding / synapse / calcium ion binding / perinuclear region of cytoplasm / enzyme binding / Golgi apparatus / protein homodimerization activity / protein-containing complex / mitochondrion / nucleoplasm / ATP binding / identical protein binding / membrane / cytoplasm / cytosol 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: 3.56 Å | ||||||
![]() | Weninger, G. / Marks, A.R. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into the regulation of RyR1 by S100A1. 著者: Gunnar Weninger / Marco C Miotto / Carl Tchagou / Steven Reiken / Haikel Dridi / Sören Brandenburg / Gabriel C Riedemann / Qi Yuan / Yang Liu / Alexander Chang / Anetta Wronska / Stephan E ...著者: Gunnar Weninger / Marco C Miotto / Carl Tchagou / Steven Reiken / Haikel Dridi / Sören Brandenburg / Gabriel C Riedemann / Qi Yuan / Yang Liu / Alexander Chang / Anetta Wronska / Stephan E Lehnart / Andrew R Marks / ![]() ![]() 要旨: S100A1, a small homodimeric EF-hand Ca-binding protein (~21 kDa), plays an important regulatory role in Ca signaling pathways involved in various biological functions including Ca cycling and ...S100A1, a small homodimeric EF-hand Ca-binding protein (~21 kDa), plays an important regulatory role in Ca signaling pathways involved in various biological functions including Ca cycling and contractile performance in skeletal and cardiac myocytes. One key target of the S100A1 interactome is the ryanodine receptor (RyR), a huge homotetrameric Ca release channel (~2.3 MDa) of the sarcoplasmic reticulum. Here, we report cryoelectron microscopy structures of S100A1 bound to RyR1, the skeletal muscle isoform, in absence and presence of Ca. Ca-free apo-S100A1 binds beneath the bridging solenoid (BSol) and forms contacts with the junctional solenoid and the shell-core linker of RyR1. Upon Ca-binding, S100A1 undergoes a conformational change resulting in the exposure of the hydrophobic pocket known to serve as a major interaction site of S100A1. Through interactions of the hydrophobic pocket with RyR1, Ca-bound S100A1 intrudes deeper into the RyR1 structure beneath BSol than the apo-form and induces sideways motions of the C-terminal BSol region toward the adjacent RyR1 protomer resulting in tighter interprotomer contacts. Interestingly, the second hydrophobic pocket of the S100A1-dimer is largely exposed at the hydrophilic surface making it prone to interactions with the local environment, suggesting that S100A1 could be involved in forming larger heterocomplexes of RyRs with other protein partners. Since S100A1 interactions stabilizing BSol are implicated in the regulation of RyR-mediated Ca release, the characterization of the S100A1 binding site conserved between RyR isoforms may provide the structural basis for the development of therapeutic strategies regarding treatments of RyR-related disorders. | ||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 3.1 MB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.2 MB | 表示 | |
XML形式データ | ![]() | 439.8 KB | 表示 | |
CIF形式データ | ![]() | 674.3 KB | 表示 | |
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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
-タンパク質 , 3種, 16分子 EFGHIJKLNMOPDABC
#1: タンパク質 | 分子量: 11939.629 Da / 分子数: 4 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #2: タンパク質 | 分子量: 10516.784 Da / 分子数: 8 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() #3: タンパク質 | 分子量: 565692.562 Da / 分子数: 4 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
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-非ポリマー , 5種, 44分子 ![](data/chem/img/CA.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/CFF.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/PCW.gif)
![](data/chem/img/ZN.gif)
![](data/chem/img/CFF.gif)
![](data/chem/img/ATP.gif)
![](data/chem/img/PCW.gif)
#4: 化合物 | ChemComp-CA / #5: 化合物 | ChemComp-ZN / #6: 化合物 | ChemComp-CFF / #7: 化合物 | ChemComp-ATP / #8: 化合物 | ChemComp-PCW / |
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-詳細
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 |
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試料調製
構成要素 | 名称: Complex of RyR1 with Calstabin-1 and S100A1 (high-Ca2+/CFF/ATP condition) タイプ: COMPLEX / 詳細: 0.25 mM free Ca2+; 5 mM Caffeine; 10 mM ATP / Entity ID: #1-#3 / 由来: NATURAL | |||||||||||||||||||||||||||||||||||
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由来(天然) | 生物種: ![]() ![]() | |||||||||||||||||||||||||||||||||||
緩衝液 | pH: 7.4 | |||||||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 8.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: 0.15 mmol/L S100A1-dimer | |||||||||||||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R0.6/1 | |||||||||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277.15 K |
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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 / 最大 デフォーカス(公称値): 1200 nm / 最小 デフォーカス(公称値): 500 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 58 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 12555 |
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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: 3.56 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 31572 / 対称性のタイプ: POINT |