+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7y89 | |||||||||
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タイトル | Structure of the GPR17-Gi complex | |||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / classA GPCR / complex | |||||||||
機能・相同性 | 機能・相同性情報 : / Leukotriene receptors / P2Y receptors / chemokine receptor activity / receptor serine/threonine kinase binding / positive regulation of Rho protein signal transduction / oligodendrocyte differentiation / plasma membrane => GO:0005886 / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex ...: / Leukotriene receptors / P2Y receptors / chemokine receptor activity / receptor serine/threonine kinase binding / positive regulation of Rho protein signal transduction / oligodendrocyte differentiation / plasma membrane => GO:0005886 / Adenylate cyclase inhibitory pathway / 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 / negative regulation of inflammatory response to antigenic stimulus / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / 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 / GDP binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / G alpha (i) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction / extracellular exosome / nucleoplasm / membrane / plasma membrane / cytoplasm / cytosol 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: 3.02 Å | |||||||||
データ登録者 | Ye, F. / Chen, G. | |||||||||
資金援助 | 1件
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引用 | ジャーナル: MedComm (2020) / 年: 2022 タイトル: Cryo-EM structure of G-protein-coupled receptor GPR17 in complex with inhibitory G protein. 著者: Fang Ye / Thian-Sze Wong / Geng Chen / Zhiyi Zhang / Binghao Zhang / Shiyi Gan / Wei Gao / Jiancheng Li / Zhangsong Wu / Xin Pan / Yang Du / 要旨: GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the ...GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling of GPR17 occurs through the heterotrimeric Gi, but its activation mechanism is unclear. Here, we employed cryo-electron microscopy (cryo-EM) technology to elucidate the structure of activated GPR17-Gi complex. The 3.02 Å resolution structure, together with mutagenesis studies, revealed that the extracellular loop2 of GPR17 occupied the orthosteric binding pocket to promote its self-activation. The active GPR17 carried several typical microswitches like other class A GPCRs. Moreover, the Gi interacted with the key residues of transmembrane helix 3 (TM3), the amphipathic helix 8 (Helix8), and intracellular loops 3 (ICL3) in GPR17 to engage in the receptor core. In summary, our results highlight the activation mechanism of GPR17 from the structural basis. Elucidating the structural and activation mechanism of GPR17 may facilitate the pharmacological intervention for acute/chronic CNS injury. | |||||||||
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 | 7y89.cif.gz | 203.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7y89.ent.gz | 160.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7y89.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 | 7y89_validation.pdf.gz | 949 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7y89_full_validation.pdf.gz | 965.7 KB | 表示 | |
XML形式データ | 7y89_validation.xml.gz | 41.6 KB | 表示 | |
CIF形式データ | 7y89_validation.cif.gz | 62.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/y8/7y89 ftp://data.pdbj.org/pub/pdb/validation_reports/y8/7y89 | HTTPS FTP |
-関連構造データ
関連構造データ | 33682MC 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
#1: タンパク質 | 分子量: 40153.672 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P63096 |
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#2: タンパク質 | 分子量: 37069.543 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62873 |
#3: タンパク質 | 分子量: 6218.162 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#4: 抗体 | 分子量: 26424.385 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#5: タンパク質 | 分子量: 33067.391 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Mus musculus (ハツカネズミ) / 参照: UniProt: Q13304 |
-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: CELL / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: GPR17-Gi / タイプ: COMPLEX / Entity ID: all / 由来: NATURAL |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.4 |
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: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1400 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 57 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: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.02 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 314674 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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