+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7td2 | ||||||||||||
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タイトル | Lysophosphatidic acid receptor 1-Gi complex bound to LPA, state a | ||||||||||||
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 / cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / Extra-nuclear estrogen signaling ...Adenylate cyclase inhibitory pathway / cellular response to 1-oleoyl-sn-glycerol 3-phosphate / lysophosphatidic acid receptor activity / positive regulation of smooth muscle cell chemotaxis / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / Lysosphingolipid and LPA receptors / : / lysophosphatidic acid binding / 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) / negative regulation of cilium assembly / G alpha (i) signalling events / regulation of synaptic vesicle cycle / bleb assembly / corpus callosum development / oligodendrocyte development / cellular response to oxygen levels / Activation of the phototransduction cascade / regulation of metabolic process / regulation of postsynaptic neurotransmitter receptor internalization / negative regulation of cAMP-mediated signaling / GTPase activating protein binding / negative regulation of synaptic transmission / 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 / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / optic nerve development / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of Rho protein signal transduction / positive regulation of dendritic spine development / : / G-protein alpha-subunit binding / GABA-ergic synapse / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / positive regulation of stress fiber assembly / myelination / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebellum development / neurogenesis / cell chemotaxis / dendritic shaft / PDZ domain binding / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GDP binding / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / negative regulation of neuron projection development / presynaptic membrane / cell cortex / regulation of cell shape / midbody / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / G alpha (q) signalling events / postsynaptic membrane / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / dendritic spine / endosome / positive regulation of apoptotic process / cell cycle / G protein-coupled receptor signaling pathway 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) Bos taurus (ウシ) Rattus norvegicus (ドブネズミ) | ||||||||||||
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: 3.11 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 | 7td2.cif.gz | 292.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7td2.ent.gz | 245.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7td2.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 | 7td2_validation.pdf.gz | 744.3 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7td2_full_validation.pdf.gz | 746.3 KB | 表示 | |
XML形式データ | 7td2_validation.xml.gz | 27.6 KB | 表示 | |
CIF形式データ | 7td2_validation.cif.gz | 41.6 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/td/7td2 ftp://data.pdbj.org/pub/pdb/validation_reports/td/7td2 | 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
#1: タンパク質 | 分子量: 39734.605 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: LPAR1, EDG2, LPA1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q92633 |
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#2: 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 |
#3: 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 |
#4: 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 |
#5: 化合物 | ChemComp-NKP / ( |
研究の焦点であるリガンドがあるか | 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 Lysophosphatidic Acid Receptor 1 with G-protein and LPA 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): 2200 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 28.2 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: 3.11 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 32504 / 対称性のタイプ: POINT |