+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7td3 | ||||||||||||
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タイトル | Sphingosine-1-phosphate receptor 1-Gi complex bound to S1P | ||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / GPCR / complex / lipid | ||||||||||||
機能・相同性 | 機能・相同性情報 Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / Extra-nuclear estrogen signaling / Olfactory Signaling Pathway ...Adenylate cyclase inhibitory pathway / cardiac muscle tissue growth involved in heart morphogenesis / Adrenaline,noradrenaline inhibits insulin secretion / sphingosine-1-phosphate receptor activity / ADP signalling through P2Y purinoceptor 12 / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / Extra-nuclear estrogen signaling / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G alpha (i) signalling events / endothelial cell differentiation / heart trabecula morphogenesis / Activation of the phototransduction cascade / regulation of bone mineralization / regulation of metabolic process / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / GTPase activating protein binding / regulation of bone resorption / negative regulation of synaptic transmission / lamellipodium assembly / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / positive regulation of positive chemotaxis / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / negative regulation of stress fiber assembly / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / transmission of nerve impulse / T cell migration / D2 dopamine receptor binding / positive regulation of protein localization to cell cortex / regulation of cell adhesion / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of smooth muscle cell proliferation / brain development / neuron differentiation / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / chemotaxis / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell migration / signaling receptor complex adaptor activity / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / midbody / actin cytoskeleton organization / angiogenesis / Interleukin-4 and Interleukin-13 signaling / Potential therapeutics for SARS / cell population proliferation / cell adhesion / endosome / positive regulation of cell migration / G protein-coupled receptor signaling pathway / membrane raft / external side of plasma membrane / cell division / intracellular membrane-bounded organelle / GTPase activity / centrosome / GTP binding / nucleolus / magnesium ion binding 類似検索 - 分子機能 | ||||||||||||
生物種 | Bos taurus (ウシ) Rattus norvegicus (ドブネズミ) 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 Å | ||||||||||||
データ登録者 | Liu, S. / Paknejad, N. / Zhu, L. / Kihara, Y. / Ray, D. / Chun, J. / Liu, W. / Hite, R.K. / Huang, X.Y. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2022 タイトル: Differential activation mechanisms of lipid GPCRs by lysophosphatidic acid and sphingosine 1-phosphate. 著者: Shian Liu / Navid Paknejad / Lan Zhu / Yasuyuki Kihara / Manisha Ray / Jerold Chun / Wei Liu / Richard K Hite / Xin-Yun Huang / 要旨: Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). ...Lysophospholipids are bioactive lipids and can signal through G-protein-coupled receptors (GPCRs). The best studied lysophospholipids are lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). The mechanisms of lysophospholipid recognition by an active GPCR, and the activations of lysophospholipid GPCR-G-protein complexes remain unclear. Here we report single-particle cryo-EM structures of human S1P receptor 1 (S1P) and heterotrimeric G complexes formed with bound S1P or the multiple sclerosis (MS) treatment drug Siponimod, as well as human LPA receptor 1 (LPA) and G complexes in the presence of LPA. Our structural and functional data provide insights into how LPA and S1P adopt different conformations to interact with their cognate GPCRs, the selectivity of the homologous lipid GPCRs for S1P versus LPA, and the different activation mechanisms of these GPCRs by LPA and S1P. Our studies also reveal specific optimization strategies to improve the MS-treating S1P-targeting drugs. | ||||||||||||
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 | 7td3.cif.gz | 193.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7td3.ent.gz | 144.5 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7td3.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 | 7td3_validation.pdf.gz | 757.6 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7td3_full_validation.pdf.gz | 760.9 KB | 表示 | |
XML形式データ | 7td3_validation.xml.gz | 29 KB | 表示 | |
CIF形式データ | 7td3_validation.cif.gz | 44.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/td/7td3 ftp://data.pdbj.org/pub/pdb/validation_reports/td/7td3 | 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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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 BAG
#1: タンパク質 | 分子量: 37416.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62871 |
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#2: タンパク質 | 分子量: 43163.070 Da / 分子数: 1 / Mutation: G203A / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnai1, Gnai-1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: B2RSH2 |
#3: タンパク質 | 分子量: 7845.078 Da / 分子数: 1 / Mutation: C68S / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63212 |
-タンパク質 / 非ポリマー / 糖 , 3種, 3分子 R
#4: タンパク質 | 分子量: 43938.734 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: S1PR1, CHEDG1, EDG1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P21453 |
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#5: 化合物 | ChemComp-S1P / ( |
#6: 糖 | ChemComp-NAG / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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Has protein modification | Y |
-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: complex of Sphingosine-1-phosphate receptor 1 with G-protein and S1P タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES | ||||||||||||||||
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7 | ||||||||||||||||
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): 1500 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 24.65 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k 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 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 449331 / 対称性のタイプ: POINT |