+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-60096 | |||||||||
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タイトル | Human GPR103 -Gq complex bound to QRFP26 | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex | |||||||||
機能・相同性 | 機能・相同性情報 orexigenic neuropeptide QRFP receptor binding / neuropeptide Y receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / regulation of feeding behavior / sensory perception of chemical stimulus / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / grooming behavior / mu-type opioid receptor binding ...orexigenic neuropeptide QRFP receptor binding / neuropeptide Y receptor activity / Orexin and neuropeptides FF and QRFP bind to their respective receptors / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / regulation of feeding behavior / sensory perception of chemical stimulus / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / grooming behavior / mu-type opioid receptor binding / positive regulation of urine volume / corticotropin-releasing hormone receptor 1 binding / positive regulation of blood pressure / negative regulation of adenylate cyclase activity / neuropeptide hormone 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 / positive regulation of neural precursor cell proliferation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / 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 / Glucagon-type ligand receptors / G alpha (i) signalling events / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / beta-2 adrenergic receptor binding / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / PKA activation in glucagon signalling / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / developmental growth / photoreceptor outer segment / neuropeptide signaling pathway / D1 dopamine receptor binding / Adenylate cyclase inhibitory pathway / Hedgehog 'off' state / positive regulation of insulin receptor signaling pathway / cellular response to hormone stimulus / positive regulation of vascular associated smooth muscle cell proliferation / cardiac muscle cell apoptotic process / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / adenylate cyclase activator activity / photoreceptor inner segment / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to nutrient / positive regulation of superoxide anion generation / Regulation of insulin secretion / locomotory behavior / G protein-coupled receptor binding / G protein-coupled receptor activity / peptide binding / bone development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating 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-coupled acetylcholine receptor signaling pathway / G-protein activation 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) / Rattus norvegicus (ドブネズミ) / Bos taurus (ウシ) / Mus musculus (ハツカネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.19 Å | |||||||||
データ登録者 | Iwama A / Akasaka H / Sano FK / Oshima HS / Shihoya W / Nureki O | |||||||||
資金援助 | 日本, 1件
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引用 | ジャーナル: Nat Commun / 年: 2024 タイトル: Structure and dynamics of the pyroglutamylated RF-amide peptide QRFP receptor GPR103. 著者: Aika Iwama / Ryoji Kise / Hiroaki Akasaka / Fumiya K Sano / Hidetaka S Oshima / Asuka Inoue / Wataru Shihoya / Osamu Nureki / 要旨: Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various ...Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various physiological functions such as energy metabolism and appetite regulation. Here, we report the cryo-electron microscopy structure of the QRFP26-GPR103-G complex at 3.19 Å resolution. QRFP26 adopts an extended structure bearing no secondary structure, with its N-terminal and C-terminal sides recognized by extracellular and transmembrane domains of GPR103 respectively. This movement, reminiscent of class B1 GPCRs except for orientation and structure of the ligand, is critical for the high-affinity binding and receptor specificity of QRFP26. Mutagenesis experiments validate the functional importance of the binding mode of QRFP26 by GPR103. Structural comparisons with closely related receptors, including RY-amide peptide-recognizing GPCRs, revealed conserved and diversified peptide recognition mechanisms, providing profound insights into the biological significance of RF-amide peptides. Collectively, this study not only advances our understanding of GPCR-ligand interactions, but also paves the way for the development of novel therapeutics targeting metabolic and appetite disorders and emergency medical care. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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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_60096.map.gz | 33.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-60096-v30.xml emd-60096.xml | 20.7 KB 20.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_60096.png | 76 KB | ||
Filedesc metadata | emd-60096.cif.gz | 6.7 KB | ||
その他 | emd_60096_half_map_1.map.gz emd_60096_half_map_2.map.gz | 32.4 MB 32.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-60096 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-60096 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_60096_validation.pdf.gz | 707.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_60096_full_validation.pdf.gz | 707.5 KB | 表示 | |
XML形式データ | emd_60096_validation.xml.gz | 12.8 KB | 表示 | |
CIF形式データ | emd_60096_validation.cif.gz | 15 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60096 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-60096 | HTTPS FTP |
-関連構造データ
関連構造データ | 8zh8MC M: このマップから作成された原子モデル 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
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 |
-マップ
ファイル | ダウンロード / ファイル: emd_60096.map.gz / 形式: CCP4 / 大きさ: 67 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: 1.0215 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
ファイル | emd_60096_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_60096_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 |
-試料の構成要素
-全体 : Human GPR103 -Gq complex bound to QRFP26
全体 | 名称: Human GPR103 -Gq complex bound to QRFP26 |
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要素 |
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-超分子 #1: Human GPR103 -Gq complex bound to QRFP26
超分子 | 名称: Human GPR103 -Gq complex bound to QRFP26 / 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: Pyroglutamylated RF-amide peptide receptor
分子 | 名称: Pyroglutamylated RF-amide peptide receptor / タイプ: protein_or_peptide / ID: 1 / 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: 45.652039 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKQALNIT PEQFSRLLRD HNLTREQFIA LYRLRPLVYT PELPGRAKLA LVLTGVLIFA LALFGNALV FYVVTRSKAM RTVTNIFICS LALSDLLITF FCIPVTMLQN ISDNWLGGAF ICKMVPFVQS TAVVTEILTM T CIAVERHQ ...文字列: MKTIIALSYI FCLVFADYKD DDDKQALNIT PEQFSRLLRD HNLTREQFIA LYRLRPLVYT PELPGRAKLA LVLTGVLIFA LALFGNALV FYVVTRSKAM RTVTNIFICS LALSDLLITF FCIPVTMLQN ISDNWLGGAF ICKMVPFVQS TAVVTEILTM T CIAVERHQ GLVHPFKMKW QYTNRRAFTM LGVVWLVAVI VGSPMWHVQQ LEIKYDFLYE KEHICCLEEW TSPVHQKIYT TF ILVILFL LPLMVMLILY SKIGYELWIK KRVGDGSVLR TIHGKEMSKI ARKKKRAVIM MVTVVALFAV CWAPFHVVHM MIE YSNFEK EYDDVTIKMI FAIVQIIGFS NSICNPIVYA FMNENFKKNV LSAVCYCIVN KTFSPAQRHG NSGSGGGGSG GSSS GG UniProtKB: Pyroglutamylated RF-amide peptide receptor |
-分子 #2: nanobody Nb35
分子 | 名称: nanobody Nb35 / 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: Lama glama (ラマ) |
分子量 | 理論値: 15.015728 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MGQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SLHHHHHH |
-分子 #3: 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: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 38.744371 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
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 LKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: 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: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Bos taurus (ウシ) |
分子量 | 理論値: 7.547685 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: 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,Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas 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: Homo sapiens (ヒト) |
分子量 | 理論値: 36.573531 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGSTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG ...文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI LGSAGSAGSA MGSTVSAED KAAAERSKMI DKNLREDGEK ARRTLRLLLL GADNSGKSTI VKQMRILHGG SGGSGGTSGI FETKFQVDKV N FHMFDVGG QRDERRKWIQ CFNDVTAIIF VVDSSDYNRL QEALNDFKSI WNNRWLRTIS VILFLNKQDL LAEKVLAGKS KI EDYFPEF ARYTTPEDAT PEPGEDPRVT RAKYFIRKEF VDISTASGDG RHICYPHFTC AVDTENARRI FNDCKDIILQ MNL REYNLV UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Guanine nucleotide-binding protein G(i) subunit alpha-2, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas |
-分子 #6: scFv16
分子 | 名称: scFv16 / 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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 27.720795 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAAASSEDL YFQ |
-分子 #7: QRF-amide
分子 | 名称: QRF-amide / タイプ: protein_or_peptide / ID: 7 / 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: 2.835161 KDa |
配列 | 文字列: TSGPLGNLAE ELNGYSRKKG GFSFRF(NH2) UniProtKB: Orexigenic neuropeptide QRFP |
-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 |
-試料調製
緩衝液 | pH: 8 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 0.83 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.6 µm / 最小 デフォーカス(公称値): 0.8 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: NONE |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.19 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 142831 |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |