+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7xk2 | ||||||||||||||||||
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タイトル | Cryo-EM Structure of Human Niacin Receptor HCA2-Gi protein complex | ||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Niacin receptor / hydroxycarboxylic acid receptor 2 / HCA2 / Gi complex | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding ...nicotinic acid receptor activity / Hydroxycarboxylic acid-binding receptors / neutrophil apoptotic process / positive regulation of neutrophil apoptotic process / Class A/1 (Rhodopsin-like receptors) / positive regulation of adiponectin secretion / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / negative regulation of lipid catabolic process / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Regulation of insulin secretion / G protein-coupled receptor binding / 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 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / response to peptide hormone / 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 / 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 / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / cell junction / 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 / fibroblast proliferation / 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 / lysosomal membrane / cell division / 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) | ||||||||||||||||||
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: 3.1 Å | ||||||||||||||||||
データ登録者 | Yang, Y. / Kang, H.J. / Gao, R.G. / Wang, J.J. / Han, G.W. / DiBerto, J.F. / Wu, L.J. / Tong, J.H. / Qu, L. / Wu, Y.R. ...Yang, Y. / Kang, H.J. / Gao, R.G. / Wang, J.J. / Han, G.W. / DiBerto, J.F. / Wu, L.J. / Tong, J.H. / Qu, L. / Wu, Y.R. / Pileski, R. / Li, X.M. / Zhang, X.C. / Zhao, S.W. / Kenakin, T. / Wang, Q. / Stevens, R.C. / Peng, W. / Roth, B.L. / Rao, Z.H. / Liu, Z.J. | ||||||||||||||||||
資金援助 | 中国, 5件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Structural insights into the human niacin receptor HCA2-G signalling complex. 著者: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao / ...著者: Yang Yang / Hye Jin Kang / Ruogu Gao / Jingjing Wang / Gye Won Han / Jeffrey F DiBerto / Lijie Wu / Jiahui Tong / Lu Qu / Yiran Wu / Ryan Pileski / Xuemei Li / Xuejun Cai Zhang / Suwen Zhao / Terry Kenakin / Quan Wang / Raymond C Stevens / Wei Peng / Bryan L Roth / Zihe Rao / Zhi-Jie Liu / 要旨: The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. ...The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors. | ||||||||||||||||||
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 | 7xk2.cif.gz | 235.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7xk2.ent.gz | 182.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7xk2.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 | 7xk2_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7xk2_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7xk2_validation.xml.gz | 45.7 KB | 表示 | |
CIF形式データ | 7xk2_validation.cif.gz | 67.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/xk/7xk2 ftp://data.pdbj.org/pub/pdb/validation_reports/xk/7xk2 | HTTPS FTP |
-関連構造データ
関連構造データ | 33241MC 7zl9C 7zlyC 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 ABC
#1: タンパク質 | 分子量: 40559.160 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): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P63096 |
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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) Homo sapiens (ヒト) / 遺伝子: GNB1 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62873 |
#5: 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 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P59768 |
-タンパク質 / 抗体 / 非ポリマー , 3種, 3分子 RS
#3: タンパク質 | 分子量: 38010.254 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: HCAR2 / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q8TDS4 |
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#4: 抗体 | 分子量: 26466.486 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) |
#6: 化合物 | ChemComp-FI7 / |
-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: Niacin Receptor HCA2-Gi complex / タイプ: COMPLEX / Entity ID: #1-#2, #4-#5 / 由来: RECOMBINANT |
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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 | 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): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 60 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-解析
ソフトウェア |
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EMソフトウェア | 名称: cryoSPARC / カテゴリ: 最終オイラー角割当 | ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 273841 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: THROUGHOUT | ||||||||||||||||||||||||
原子変位パラメータ | Biso max: 175.49 Å2 / Biso mean: 71.6689 Å2 / Biso min: 5.36 Å2 | ||||||||||||||||||||||||
拘束条件 |
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