+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8h8j | ||||||
---|---|---|---|---|---|---|---|
タイトル | Lodoxamide-bound GPR35 in complex with G13 | ||||||
要素 |
| ||||||
キーワード | MEMBRANE PROTEIN (膜タンパク質) / GPR35 / G13 / Lodoxamide | ||||||
機能・相同性 | 機能・相同性情報 negative regulation of neuronal action potential / : / D5 dopamine receptor binding / regulation of fibroblast migration / C-X-C chemokine receptor activity / negative regulation of voltage-gated calcium channel activity / negative regulation of vascular associated smooth muscle cell migration / Class A/1 (Rhodopsin-like receptors) / chemokine-mediated signaling pathway / regulation of small GTPase mediated signal transduction ...negative regulation of neuronal action potential / : / D5 dopamine receptor binding / regulation of fibroblast migration / C-X-C chemokine receptor activity / negative regulation of voltage-gated calcium channel activity / negative regulation of vascular associated smooth muscle cell migration / Class A/1 (Rhodopsin-like receptors) / chemokine-mediated signaling pathway / regulation of small GTPase mediated signal transduction / branching involved in blood vessel morphogenesis / positive regulation of Rho protein signal transduction / NRAGE signals death through JNK / negative regulation of vascular associated smooth muscle cell proliferation / CDC42 GTPase cycle / Rho protein signal transduction / cytoskeleton organization / RAC1 GTPase cycle / guanyl-nucleotide exchange factor activity / 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 / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / 凝固・線溶系 / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / 血圧 / 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 / メラノソーム / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / regulation of cell shape / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / in utero embryonic development / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / 細胞分化 / G protein-coupled receptor signaling pathway / lysosomal membrane / focal adhesion / GTPase activity / シナプス / protein-containing complex binding / GTP binding / シグナル伝達 / extracellular exosome / 生体膜 / metal ion binding / 細胞核 / 細胞膜 / 細胞質基質 / 細胞質 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: 3.2 Å | ||||||
データ登録者 | Yuan, Q. / Duan, J. / Liu, Q. / Xu, H.E. / Jiang, Y. | ||||||
資金援助 | 中国, 1件
| ||||||
引用 | ジャーナル: Cell Discov / 年: 2022 タイトル: Insights into divalent cation regulation and G-coupling of orphan receptor GPR35. 著者: Jia Duan / Qiufeng Liu / Qingning Yuan / Yujie Ji / Shengnan Zhu / Yangxia Tan / Xinheng He / Youwei Xu / Jingjing Shi / Xi Cheng / Hualiang Jiang / H Eric Xu / Yi Jiang / 要旨: Endogenous ions play important roles in the function and pharmacology of G protein-coupled receptors (GPCRs) with limited atomic evidence. In addition, compared with G protein subtypes G, G, and G, ...Endogenous ions play important roles in the function and pharmacology of G protein-coupled receptors (GPCRs) with limited atomic evidence. In addition, compared with G protein subtypes G, G, and G, insufficient structural evidence is accessible to understand the coupling mechanism of G protein by GPCRs. Orphan receptor GPR35, which is predominantly expressed in the gastrointestinal tract and is closely related to inflammatory bowel diseases (IBDs), stands out as a prototypical receptor for investigating ionic modulation and G coupling. Here we report a cryo-electron microscopy structure of G-coupled GPR35 bound to an anti-allergic drug, lodoxamide. This structure reveals a novel divalent cation coordination site and a unique ionic regulatory mode of GPR35 and also presents a highly positively charged binding pocket and the complementary electrostatic ligand recognition mode, which explain the promiscuity of acidic ligand binding by GPR35. Structural comparison of the GPR35-G complex with other G protein subtypes-coupled GPCRs reveals a notable movement of the C-terminus of α5 helix of the Gα subunit towards the receptor core and the least outward displacement of the cytoplasmic end of GPR35 TM6. A featured 'methionine pocket' contributes to the G coupling by GPR35. Together, our findings provide a structural basis for divalent cation modulation, ligand recognition, and subsequent G protein coupling of GPR35 and offer a new opportunity for designing GPR35-targeted drugs for the treatment of IBDs. | ||||||
履歴 |
|
-構造の表示
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 | 8h8j.cif.gz | 215.8 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8h8j.ent.gz | 164.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8h8j.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/h8/8h8j ftp://data.pdbj.org/pub/pdb/validation_reports/h8/8h8j | HTTPS FTP |
---|
-関連構造データ
関連構造データ | 34549MC 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) |
---|---|
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 |
|
---|---|
1 |
|
-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 42423.633 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 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q14344 |
---|---|
#2: タンパク質 | 分子量: 40226.992 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 |
-タンパク質 / 抗体 , 2種, 2分子 CH
#3: タンパク質 | 分子量: 33972.047 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: GPR35 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q9HC97 |
---|---|
#5: 抗体 | 分子量: 26277.299 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) |
-非ポリマー , 3種, 5分子
#6: 化合物 | ChemComp-WYB / |
---|---|
#7: 化合物 | ChemComp-CA / |
#8: 化合物 |
-詳細
研究の焦点であるリガンドがあるか | N |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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: Lodoxamide-GPR35-G13 complex / タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.04 |
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 |
---|---|
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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 800 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
---|---|
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 591246 / 対称性のタイプ: POINT |