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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 8k6n | |||||||||||||||||||||||||||||||||||||||||||||
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| タイトル | Structural complex of neuropeptide Y receptor 2 | |||||||||||||||||||||||||||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / neuropeptide Y receptor 2 / complex | |||||||||||||||||||||||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報negative regulation of nervous system process / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process ...negative regulation of nervous system process / regulation of nerve growth factor production / peptide YY receptor activity / short-day photoperiodism / negative regulation of acute inflammatory response to antigenic stimulus / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of peptide secretion / neuropeptide Y receptor activity / monocyte activation / positive regulation of dopamine metabolic process / : / positive regulation of appetite / neuropeptide Y receptor binding / intestinal epithelial cell differentiation / positive regulation of eating behavior / negative regulation of secretion / synaptic signaling via neuropeptide / cardiac left ventricle morphogenesis / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / adult feeding behavior / positive regulation of smooth muscle contraction / regulation of presynaptic cytosolic calcium ion concentration / negative regulation of calcium ion-dependent exocytosis / negative regulation of excitatory postsynaptic potential / positive regulation of dopamine secretion / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / neuropeptide hormone activity / positive regulation of urine volume / positive regulation of neural precursor cell proliferation / feeding behavior / negative regulation of cAMP/PKA signal transduction / negative regulation of synaptic transmission / non-motile cilium / negative regulation of synaptic transmission, glutamatergic / positive regulation of cell-substrate adhesion / negative regulation of feeding behavior / gamma-aminobutyric acid signaling pathway / regulation of synaptic vesicle exocytosis / central nervous system neuron development / outflow tract morphogenesis / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / nitric oxide mediated signal transduction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / behavioral fear response / neuronal dense core vesicle / Adenylate cyclase inhibitory pathway / negative regulation of blood pressure / positive regulation of vascular associated smooth muscle cell proliferation / positive regulation of superoxide anion generation / response to nutrient / Peptide ligand-binding receptors / hippocampal mossy fiber to CA3 synapse / calcium channel regulator activity / Regulation of insulin secretion / locomotory behavior / G protein-coupled receptor binding / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cerebral cortex development / GABA-ergic synapse / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / terminal bouton / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / neuron projection development / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding 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: 3.2 Å | |||||||||||||||||||||||||||||||||||||||||||||
データ登録者 | Shen, S.Y. / Zhao, C. / Shao, Z.H. | |||||||||||||||||||||||||||||||||||||||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: MedComm (2020) / 年: 2024タイトル: Structural basis of neuropeptide Y signaling through Y and Y receptors. 著者: Siyuan Shen / Yue Deng / Chenglong Shen / Haidi Chen / Lin Cheng / Chao Wu / Chang Zhao / Zhiqian Yang / Hanlin Hou / Kexin Wang / Zhenhua Shao / Cheng Deng / Feng Ye / Wei Yan / ![]() 要旨: Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs ...Neuropeptide Y (NPY), a 36-amino-acid peptide, functions as a neurotransmitter in both the central and peripheral nervous systems by activating the NPY receptor subfamily. Notably, NPY analogs display varying selectivity and exert diverse physiological effects through their interactions with this receptor family. [Pro]-NPY and [Leu, Pro]-NPY, mainly acting on YR, reportedly increases blood pressure and postsynaptically potentiates the effect of other vasoactive substances above all, while N-terminal cleaved NPY variants in human body primary mediates angiogenesis and neurotransmitter release inhibition through YR. However, the recognition mechanisms of YR and YR with specific agonists remain elusive, thereby hindering subtype receptor-selective drug development. In this study, we report three cryo-electron microscopy (cryo-EM) structures of Gi2-coupled YR and YR in complexes with NPY, as well as YR bound to a selective agonist [Leu, Pro]-NPY. Combined with cell-based assays, our study not only reveals the conserved peptide-binding mode of NPY receptors but also identifies an additional sub-pocket that confers ligand selectivity. Moreover, our analysis of YR evolutionary dynamics suggests that this sub-pocket has undergone functional adaptive evolution across different species. Collectively, our findings shed light on the molecular underpinnings of neuropeptide recognition and receptor activation, and they present a promising avenue for the design of selective drugs targeting the NPY receptor family. | |||||||||||||||||||||||||||||||||||||||||||||
| 履歴 |
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 8k6n.cif.gz | 221.2 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb8k6n.ent.gz | 171 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 8k6n.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 | 8k6n_validation.pdf.gz | 1 MB | 表示 | wwPDB検証レポート |
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| 文書・詳細版 | 8k6n_full_validation.pdf.gz | 1.1 MB | 表示 | |
| XML形式データ | 8k6n_validation.xml.gz | 42.3 KB | 表示 | |
| CIF形式データ | 8k6n_validation.cif.gz | 64.2 KB | 表示 | |
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/k6/8k6n ftp://data.pdbj.org/pub/pdb/validation_reports/k6/8k6n | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 36924MC ![]() 8k6mC ![]() 8k6oC 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 ( |
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| 類似構造データ | 類似検索 - 機能・相同性 F&H 検索 |
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リンク
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集合体
| 登録構造単位 | ![]()
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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: 40502.863 Da / 分子数: 1 / 変異: S47N,G204A,E246A,A327S / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI2, GNAI2B発現宿主: ![]() 参照: UniProt: P04899 |
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| #2: タンパク質 | 分子量: 39141.793 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: ![]() 参照: UniProt: P62873 |
| #3: 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: ![]() 参照: UniProt: P59768 |
-タンパク質・ペプチド / タンパク質 / 抗体 , 3種, 3分子 DES
| #4: タンパク質・ペプチド | 分子量: 4278.720 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P01303 |
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| #5: タンパク質 | 分子量: 38321.039 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: NPY2R発現宿主: ![]() 参照: UniProt: P49146 |
| #6: 抗体 | 分子量: 28636.793 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() |
-詳細
| Has protein modification | 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 |
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試料調製
| 構成要素 | 名称: Structural complex of neuropeptide Y receptor 1 / タイプ: COMPLEX / Entity ID: all / 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: ![]() |
| 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 |
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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): 1800 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 K2 SUMMIT (4k x 4k) |
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解析
| EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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| CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| 3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 738846 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
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ムービー
コントローラー
万見について




Homo sapiens (ヒト)

中国, 1件
引用




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FIELD EMISSION GUN