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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Cryo-EM structures of NPFFR2 complex with neuropeptide FF | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | NPFFR2 / NPFF / GPR74 / GPCR / MEMBRANE PROTEIN/IMMUNE SYSTEM / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
| 機能・相同性 | 機能・相同性情報opioid receptor binding / Orexin and neuropeptides FF and QRFP bind to their respective receptors / detection of abiotic stimulus / neuropeptide receptor activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma ...opioid receptor binding / Orexin and neuropeptides FF and QRFP bind to their respective receptors / detection of abiotic stimulus / neuropeptide receptor activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / spectrin binding / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / alkylglycerophosphoethanolamine phosphodiesterase activity / regulation of MAPK cascade / photoreceptor outer segment / cellular response to hormone stimulus / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / cardiac muscle cell apoptotic process / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / photoreceptor inner segment / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / chemokine-mediated signaling pathway / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / ADP signalling through P2Y purinoceptor 12 / GDP binding / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding / sensory perception of taste / actin cytoskeleton / adenylate cyclase-activating G protein-coupled receptor signaling pathway / sperm principal piece / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / GTPase binding 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() ![]() | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.49 Å | |||||||||
データ登録者 | Pan BX / Li XZ / Jiang Y | |||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Rep / 年: 2025タイトル: Structural basis of peptide recognition and modulation for neuropeptide FF receptors. 著者: Xinzhu Li / Heng Zhang / Wen Hu / Kai Wu / Shuai Li / Sanshan Jin / Yuling Yin / Qingning Yuan / H Eric Xu / Benxun Pan / Yi Jiang / ![]() 要旨: Neuropeptide FF receptors 1 and 2 (NPFFR1 and NPFFR2) are RF-amide peptide receptors that couple to G proteins and regulate pain, opioid tolerance, and metabolism. Despite their physiological ...Neuropeptide FF receptors 1 and 2 (NPFFR1 and NPFFR2) are RF-amide peptide receptors that couple to G proteins and regulate pain, opioid tolerance, and metabolism. Despite their physiological significance, their ligand selectivity and activation mechanisms remain unclear. Using cryoelectron microscopy, we resolved four NPFFR1 and NPFFR2 structures bound to NPFF or NPVF, revealing conserved C-terminal RF-amide interactions within the orthosteric pocket and N-terminal variations driving subtype specificity. Structural and mutagenesis analyses identified ECL2 and the receptor N terminus as key determinants of NPVF-NPFFR1 and NPFF-NPFFR2 selectivity. Additionally, the structures elucidate the activation mechanism and uncover distinct G-coupling features between NPFFR subtypes. These findings provide molecular insights into peptide recognition and receptor activation within the RF-amide family, offering a structural framework for designing selective NPFFR modulators to treat pain, addiction, and metabolic disorders with enhanced specificity and reduced off-target effects. | |||||||||
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_63578.map.gz | 89.2 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-63578-v30.xml emd-63578.xml | 25.3 KB 25.3 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_63578_fsc.xml | 11.9 KB | 表示 | FSCデータファイル |
| 画像 | emd_63578.png | 37.4 KB | ||
| マスクデータ | emd_63578_msk_1.map | 178 MB | マスクマップ | |
| Filedesc metadata | emd-63578.cif.gz | 7.6 KB | ||
| その他 | emd_63578_half_map_1.map.gz emd_63578_half_map_2.map.gz | 165.3 MB 165.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-63578 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-63578 | HTTPS FTP |
-関連構造データ
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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| 「今月の分子」の関連する項目 |
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マップ
| ファイル | ダウンロード / ファイル: emd_63578.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 0.73 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
-マスク #1
| ファイル | emd_63578_msk_1.map | ||||||||||||
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| 密度ヒストグラム |
-ハーフマップ: #2
| ファイル | emd_63578_half_map_1.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_63578_half_map_2.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
-全体 : Neuropeptide receptor 2 complex with Gi, Gbeta, Ggamma,scfv16 and...
| 全体 | 名称: Neuropeptide receptor 2 complex with Gi, Gbeta, Ggamma,scfv16 and neuropeptide FF |
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| 要素 |
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-超分子 #1: Neuropeptide receptor 2 complex with Gi, Gbeta, Ggamma,scfv16 and...
| 超分子 | 名称: Neuropeptide receptor 2 complex with Gi, Gbeta, Ggamma,scfv16 and neuropeptide FF タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Soluble cytochrome b562,Neuropeptide FF receptor 2,Neuropeptide F...
| 分子 | 名称: Soluble cytochrome b562,Neuropeptide FF receptor 2,Neuropeptide FF receptor 2 タイプ: protein_or_peptide / ID: 1 詳細: The chimera protein contains fusion protein BRIL at N-terminal,The chimera protein contains fusion protein BRIL at N-terminal,The chimera protein contains fusion protein BRIL at N- ...詳細: The chimera protein contains fusion protein BRIL at N-terminal,The chimera protein contains fusion protein BRIL at N-terminal,The chimera protein contains fusion protein BRIL at N-terminal,The chimera protein contains fusion protein BRIL at N-terminal コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 67.597008 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDG SAENLYFQGA SADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAAL DAQKATPPKL EDKSPDSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAYIQKYLMN E KWDTNSSE ...文字列: MDSKGSSQKG SRLLLLLVVS NLLLCQGVVS DYKDDDDVDG SAENLYFQGA SADLEDNWET LNDNLKVIEK ADNAAQVKDA LTKMRAAAL DAQKATPPKL EDKSPDSPEM KDFRHGFDIL VGQIDDALKL ANEGKVKEAQ AAAEQLKTTR NAYIQKYLMN E KWDTNSSE NWHPIWNVND TKHHLYSDIN ITYVNYYLHQ PQVAAIFIIS YFLIFFLCMM GNTVVCFIVM RNKHMHTVTN LF ILNLAIS DLLVGIFCMP ITLLDNIIAG WPFGNTMCKI SGLVQGISVA ASVFTLVAIA VDRFQCVVYP FKPKLTIKTA FVI IMIIWV LAITIMSPSA VMLHVQEEKY YRVRLNSQNK TSPVYWCRED WPNQEMRKIY TTVLFANIYL APLSLIVIMY GRIG ISLFR AAVPHTGRKN QEQWHVVSRK KQKIIKMLLI VALLFILSWL PLWTLMMLSD YADLSPNELQ IINIYIYPFA HWLAF GNSS VNPIIYGFFN ENFRRGFQEA FQLQLCQKRA KPMEAYALKA KSHVLINTSN QLVQESTFQN PHGETLLYRK SAEKPQ QEL VMEELKETTN SSEIHHHHHH HHHHHH UniProtKB: Neuropeptide FF receptor 2 |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 39.750277 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...文字列: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWNGSSGG GGSGGGGSSG UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: ![]() |
| 分子量 | 理論値: 7.861143 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Morphine-modulating neuropeptide B
| 分子 | 名称: Morphine-modulating neuropeptide B / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: synthetic construct (人工物) |
| 分子量 | 理論値: 1.081268 KDa |
| 配列 | 文字列: FLFQPQRF(NH2) UniProtKB: Morphine-modulating neuropeptide B |
-分子 #5: scfv16
| 分子 | 名称: scfv16 / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: synthetic construct (人工物) |
| 分子量 | 理論値: 26.277299 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL |
-分子 #6: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.445059 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
| 試料の集合状態 | particle |
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試料調製
| 緩衝液 | pH: 7.4 |
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| 凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
| 顕微鏡 | TFS KRIOS |
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| 撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 照射モード: OTHER / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 5.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
中国, 1件
引用



























Z (Sec.)
Y (Row.)
X (Col.)













































解析
FIELD EMISSION GUN


