+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7t6b | ||||||||||||
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タイトル | Structure of S1PR2-heterotrimeric G13 signaling complex | ||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN/IMMUNE SYSTEM / S1P / S1PR2 / GPCR / membrane protein / cryo-EM / SIGNALING PROTEIN-IMMUNE SYSTEM complex | ||||||||||||
機能・相同性 | 機能・相同性情報 D5 dopamine receptor binding / : / regulation of fibroblast migration / positive regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of smooth muscle cell migration / negative regulation of excitatory postsynaptic potential / negative regulation of vascular associated smooth muscle cell migration / filopodium assembly ...D5 dopamine receptor binding / : / regulation of fibroblast migration / positive regulation of establishment of endothelial barrier / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / negative regulation of smooth muscle cell migration / negative regulation of excitatory postsynaptic potential / negative regulation of vascular associated smooth muscle cell migration / filopodium assembly / G protein-coupled peptide receptor activity / regulation of metabolic process / sphingosine-1-phosphate receptor signaling pathway / regulation of small GTPase mediated signal transduction / branching involved in blood vessel morphogenesis / NRAGE signals death through JNK / negative regulation of vascular associated smooth muscle cell proliferation / CDC42 GTPase cycle / Rho protein signal transduction / RAC1 GTPase cycle / G protein activity / guanyl-nucleotide exchange factor activity / positive regulation of peptidyl-threonine phosphorylation / G protein-coupled receptor binding / G protein-coupled receptor activity / brush border membrane / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / platelet activation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / regulation of blood pressure / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / melanosome / integrin binding / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / regulation of cell shape / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / in utero embryonic development / Ras protein signal transduction / cell population proliferation / membrane => GO:0016020 / Extra-nuclear estrogen signaling / cell differentiation / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / lipid binding / synapse / positive regulation of cell population proliferation / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / nucleus 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) Mus musculus (ハツカネズミ) | ||||||||||||
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: 3.19 Å | ||||||||||||
データ登録者 | Li, X. / Chen, H. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Sci Adv / 年: 2022 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
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 | 7t6b.cif.gz | 208.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7t6b.ent.gz | 163.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7t6b.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/t6/7t6b ftp://data.pdbj.org/pub/pdb/validation_reports/t6/7t6b | HTTPS FTP |
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-関連構造データ
関連構造データ | 25712MC 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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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ACD
#1: タンパク質 | 分子量: 42255.273 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: GNA13 / 細胞株 (発現宿主): Sf9 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q14344 |
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#2: タンパク質 | 分子量: 39970.660 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: GNB1 / 細胞株 (発現宿主): Sf9 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#3: タンパク質 | 分子量: 7861.143 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: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
-抗体 / タンパク質 / 非ポリマー , 3種, 3分子 ER
#4: 抗体 | 分子量: 27784.896 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
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#5: タンパク質 | 分子量: 39902.824 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: S1PR2, EDG5 / 細胞株 (発現宿主): HEK293S GnTI- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O95136 |
#6: 化合物 | ChemComp-S1P / ( |
-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 |
-試料調製
構成要素 | 名称: Structure of S1PR2-heterotrimeric G13 signaling complex タイプ: COMPLEX / Entity ID: #1-#5 / 由来: MULTIPLE SOURCES | |||||||||||||||
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分子量 | 実験値: NO | |||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.5 詳細: 20 mM Hepes pH7.5, 150 mM NaCl, 0.001% L-MNG/0.0001% CHS, 0.0025% GDN | |||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: C-flat-1.2/1.3 | |||||||||||||||
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: DIFFRACTION / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.16_3549: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.19 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 640483 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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