+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8g94 | ||||||||||||
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タイトル | Structure of CD69-bound S1PR1 coupled to heterotrimeric Gi | ||||||||||||
要素 |
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キーワード | IMMUNE SYSTEM / CD69 / S1PR1 / Sphingosine-1-phosphate / lymphocyte egress / GPCR | ||||||||||||
機能・相同性 | 機能・相同性情報 cardiac muscle tissue growth involved in heart morphogenesis / sphingosine-1-phosphate receptor activity / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization / regulation of metabolic process ...cardiac muscle tissue growth involved in heart morphogenesis / sphingosine-1-phosphate receptor activity / sphingolipid binding / blood vessel maturation / Lysosphingolipid and LPA receptors / T cell migration / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization / regulation of metabolic process / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / regulation of bone resorption / lamellipodium assembly / positive regulation of positive chemotaxis / negative regulation of stress fiber assembly / transmission of nerve impulse / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cell adhesion / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Regulation of insulin secretion / 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 / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / brain development / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / neuron differentiation / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / 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 / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / transmembrane signaling receptor activity / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / chemotaxis / GDP binding / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / cell migration / cellular response to xenobiotic stimulus / 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 / cell cortex / midbody / G alpha (i) signalling events / actin cytoskeleton organization / fibroblast proliferation / carbohydrate binding / G alpha (s) signalling events / G alpha (q) signalling events / angiogenesis / Interleukin-4 and Interleukin-13 signaling / Ras protein signal transduction / Potential therapeutics for SARS / cell population proliferation / Extra-nuclear estrogen signaling / cell adhesion / endosome / positive regulation of cell migration 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: 3.15 Å | ||||||||||||
データ登録者 | Chen, H. / Li, X. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Elife / 年: 2023 タイトル: Transmembrane protein CD69 acts as an S1PR1 agonist. 著者: Hongwen Chen / Yu Qin / Marissa Chou / Jason G Cyster / Xiaochun Li / 要旨: The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple ...The activation of Sphingosine-1-phosphate receptor 1 (S1PR1) by S1P promotes lymphocyte egress from lymphoid organs, a process critical for immune surveillance and T cell effector activity. Multiple drugs that inhibit S1PR1 function are in use clinically for the treatment of autoimmune diseases. Cluster of Differentiation 69 (CD69) is an endogenous negative regulator of lymphocyte egress that interacts with S1PR1 in cis to facilitate internalization and degradation of the receptor. The mechanism by which CD69 causes S1PR1 internalization has been unclear. Moreover, although there are numerous class A GPCR structures determined with different small molecule agonists bound, it remains unknown whether a transmembrane protein per se can act as a class A GPCR agonist. Here, we present the cryo-EM structure of CD69-bound S1PR1 coupled to the heterotrimeric G complex. The transmembrane helix (TM) of one protomer of CD69 homodimer contacts the S1PR1-TM4. This interaction allosterically induces the movement of S1PR1-TMs 5-6, directly activating the receptor to engage the heterotrimeric G. Mutations in key residues at the interface affect the interactions between CD69 and S1PR1, as well as reduce the receptor internalization. Thus, our structural findings along with functional analyses demonstrate that CD69 acts in cis as a protein agonist of S1PR1, thereby promoting G-dependent S1PR1 internalization, loss of S1P gradient sensing, and inhibition of lymphocyte egress. | ||||||||||||
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 | 8g94.cif.gz | 223 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8g94.ent.gz | 173 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8g94.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 | 8g94_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8g94_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 8g94_validation.xml.gz | 45.9 KB | 表示 | |
CIF形式データ | 8g94_validation.cif.gz | 70 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/g9/8g94 ftp://data.pdbj.org/pub/pdb/validation_reports/g9/8g94 | HTTPS FTP |
-関連構造データ
関連構造データ | 29861MC 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
-タンパク質 , 2種, 3分子 AFG
#1: タンパク質 | 分子量: 40083.781 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 / 細胞株 (発現宿主): HEK293S GnTI / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P21453 |
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#6: タンパク質 | 分子量: 23912.793 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CD69, CLEC2C / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q07108 |
-Guanine nucleotide-binding protein ... , 3種, 3分子 BCD
#2: タンパク質 | 分子量: 40445.059 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: GNAI1 / 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: P63096 |
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#3: タンパク質 | 分子量: 37728.152 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 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
#4: 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 , 1種, 1分子 E
#5: 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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-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 CD69-bound S1PR1 coupled to heterotrimeric Gi タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 値: 0.2 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293 |
緩衝液 | pH: 7.5 |
試料 | 濃度: 10 mg/ml / 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: Quantifoil R1.2/1.3 |
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: 293 K |
-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): 2500 nm / 最小 デフォーカス(公称値): 800 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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EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.15 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 293516 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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