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基本情報
登録情報 | ![]() | ||||||||||||
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タイトル | Structure of S1PR2-heterotrimeric G13 signaling complex | ||||||||||||
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![]() | S1P / S1PR2 / GPCR / membrane protein / cryo-EM / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
機能・相同性 | ![]() D5 dopamine receptor binding / positive regulation of establishment of endothelial barrier / Rho-activating G protein-coupled receptor signaling pathway / regulation of fibroblast migration / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of excitatory postsynaptic potential / filopodium assembly / sphingosine-1-phosphate receptor signaling pathway / G protein-coupled peptide receptor activity ...D5 dopamine receptor binding / positive regulation of establishment of endothelial barrier / Rho-activating G protein-coupled receptor signaling pathway / regulation of fibroblast migration / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of excitatory postsynaptic potential / filopodium assembly / sphingosine-1-phosphate receptor signaling pathway / G protein-coupled peptide receptor activity / regulation of small GTPase mediated signal transduction / regulation of metabolic process / positive regulation of peptidyl-threonine phosphorylation / NRAGE signals death through JNK / branching involved in blood vessel morphogenesis / negative regulation of vascular associated smooth muscle cell migration / negative regulation of vascular associated smooth muscle cell proliferation / CDC42 GTPase cycle / regulation of postsynapse assembly / Rho protein signal transduction / RAC1 GTPase cycle / guanyl-nucleotide exchange factor activity / excitatory postsynaptic potential / G protein-coupled receptor binding / brush border membrane / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / platelet activation / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / integrin binding / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / melanosome / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / regulation of cell shape / signaling receptor complex adaptor activity / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / actin cytoskeleton organization / positive regulation of cytosolic calcium ion concentration / GTPase binding / retina development in camera-type eye / Ca2+ pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / in utero embryonic development / Ras protein signal transduction / cell differentiation / Extra-nuclear estrogen signaling / cell population proliferation / postsynapse / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / positive regulation of cell population proliferation / synapse / lipid binding / protein-containing complex binding / GTP binding 類似検索 - 分子機能 | ||||||||||||
生物種 | ![]() ![]() ![]() | ||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.19 Å | ||||||||||||
![]() | Li X / Chen H | ||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of S1PR2-heterotrimeric G signaling complex. 著者: Hongwen Chen / Kevin Chen / Weijiao Huang / Louis M Staudt / Jason G Cyster / Xiaochun Li / ![]() 要旨: Sphingosine-1-phosphate (S1P) regulates immune cell trafficking, angiogenesis, and vascular function via its five receptors. Inherited mutations in S1P receptor 2 (S1PR2) occur in individuals with ...Sphingosine-1-phosphate (S1P) regulates immune cell trafficking, angiogenesis, and vascular function via its five receptors. Inherited mutations in S1P receptor 2 (S1PR2) occur in individuals with hearing loss, and acquired mutations in S1PR2 and G occur in a malignant lymphoma. Here, we present the cryo-electron microscopy structure of S1P-bound S1PR2 coupled to the heterotrimeric G. Interaction between S1PR2 intracellular loop 2 (ICL2) and transmembrane helix 4 confines ICL2 to engage the α5 helix of G. Transforming growth factor-α shedding assays and cell migration assays support the key roles of the residues in S1PR2-G complex assembly. The structure illuminates the mechanism of receptor disruption by disease-associated mutations. Unexpectedly, we showed that FTY720-P, an agonist of the other four S1PRs, can trigger G activation via S1PR2. S1PR2 variant can increase the activity of G considerably with FTY720-P and S1P, thus revealing a basis for S1PR drug selectivity. | ||||||||||||
履歴 |
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 85.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.2 KB 19.2 KB | 表示 表示 | ![]() |
画像 | ![]() | 46.8 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 477 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 476.6 KB | 表示 | |
XML形式データ | ![]() | 6.6 KB | 表示 | |
CIF形式データ | ![]() | 7.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7t6bMC M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.842 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : Structure of S1PR2-heterotrimeric G13 signaling complex
全体 | 名称: Structure of S1PR2-heterotrimeric G13 signaling complex |
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要素 |
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-超分子 #1: Structure of S1PR2-heterotrimeric G13 signaling complex
超分子 | 名称: Structure of S1PR2-heterotrimeric G13 signaling complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Guanine nucleotide-binding protein subunit alpha-13
分子 | 名称: Guanine nucleotide-binding protein subunit alpha-13 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 42.255273 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA ARLVKILLLG AGESGKSTFL KQMRIIHGQD FDQRAREEFR PTIYSNVIKG MRVLVDARE KLHIPWGDNS NQQHGDKMMS FDTRAPMAAQ GMVETRVFLQ YLPAIRALWA DSGIQNAYDR RREFQLGESV K YFLDNLDK ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA ARLVKILLLG AGESGKSTFL KQMRIIHGQD FDQRAREEFR PTIYSNVIKG MRVLVDARE KLHIPWGDNS NQQHGDKMMS FDTRAPMAAQ GMVETRVFLQ YLPAIRALWA DSGIQNAYDR RREFQLGESV K YFLDNLDK LGEPDYIPSQ QDILLARRPT KGIHEYDFEI KNVPFKMVDV GGQRSERKRW FECFDSVTSI LFLVSSSEFD QV LMEDRLT NRLTESLNIF ETIVNNRVFS NVSIILFLNK TDLLEEKVQV VSIKDYFLEF EGDPHCLRDV QKFLVECFRG KRR DQQQKP LYHHFTTAIN TENIRLVFRD VKDTILHDNL KQLMLQ UniProtKB: Guanine nucleotide-binding protein subunit alpha-13 |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 39.97066 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHHHH HLEVLFQGPG SSGSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAKI YAMHWGTDS RLLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK TREGNVRVSR E LAGHTGYL ...文字列: MHHHHHHHHH HLEVLFQGPG SSGSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAKI YAMHWGTDS RLLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK TREGNVRVSR E LAGHTGYL SCCRFLDDNQ IVTSSGDTTC ALWDIETGQQ TTTFTGHTGD VMSLSLAPDT RLFVSGACDA SAKLWDVREG MC RQTFTGH ESDINAICFF PNGNAFATGS DDATCRLFDL RADQELMTYS HDNIICGITS VSFSKSGRLL LAGYDDFNCN VWD ALKADR AGVLAGHDNR VSCLGVTDDG MAVATGSWDS FLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: scFv16
分子 | 名称: scFv16 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 27.784896 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAHHHHHH HH |
-分子 #5: Sphingosine 1-phosphate receptor 2
分子 | 名称: Sphingosine 1-phosphate receptor 2 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 39.902824 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGSLYSEYLN PNKVQEHYNY TKETLETQET TSRQVASAFI VILCCAIVVE NLLVLIAVAR NSKFHSAMYL FLGNLAASDL LAGVAFVAN TLLSGSVTLR LTPVQWFARE GSAFITLSAS VFSLLAIAIE RHVAIAKVKL YGSDKSCRML LLIGASWLIS L VLGGLPIL ...文字列: MGSLYSEYLN PNKVQEHYNY TKETLETQET TSRQVASAFI VILCCAIVVE NLLVLIAVAR NSKFHSAMYL FLGNLAASDL LAGVAFVAN TLLSGSVTLR LTPVQWFARE GSAFITLSAS VFSLLAIAIE RHVAIAKVKL YGSDKSCRML LLIGASWLIS L VLGGLPIL GWNCLGHLEA CSTVLPLYAK HYVLCVVTIF SIILLAIVAL YVRIYCVVRS SHADMAAPQT LALLKTVTIV LG VFIVCWL PAFSILLLDY ACPVHSCPIL YKAHYFFAVS TLNSLLNPVI YTWRSRDLRR EVLRPLQCWR PGVGVQGRRR GGT PGHHLL PLRSSSSLER GMHMPTSPTF LEGNTVVDYK DDDDK UniProtKB: Sphingosine 1-phosphate receptor 2 |
-分子 #6: (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate
分子 | 名称: (2S,3R,4E)-2-amino-3-hydroxyoctadec-4-en-1-yl dihydrogen phosphate タイプ: ligand / ID: 6 / コピー数: 1 / 式: S1P |
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分子量 | 理論値: 379.472 Da |
Chemical component information | ![]() ChemComp-S1P: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 構成要素:
詳細: 20 mM Hepes pH7.5, 150 mM NaCl, 0.001% L-MNG/0.0001% CHS, 0.0025% GDN | |||||||||
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グリッド | モデル: C-flat-1.2/1.3 / 材質: GOLD / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY | |||||||||
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DIFFRACTION / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |