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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of the relaxin receptor RXFP1 in complex with heterotrimeric Gs | |||||||||
![]() | Primary map used for model building, generated from a combine focused maps job in Phenix. | |||||||||
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![]() | GPCR / Complex / Signaling / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() lung connective tissue development / nipple morphogenesis / Relaxin receptors / parturition / myofibroblast differentiation / G protein-coupled peptide receptor activity / hormone binding / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation ...lung connective tissue development / nipple morphogenesis / Relaxin receptors / parturition / myofibroblast differentiation / G protein-coupled peptide receptor activity / hormone binding / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / activation of adenylate cyclase activity / renal water homeostasis / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / hormone-mediated signaling pathway / extracellular matrix organization / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / bone development / platelet aggregation / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / cognition / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / sensory perception of smell / 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 / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / G protein activity / GTPase binding / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | |||||||||
![]() | Erlandson SC / Rawson S | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The relaxin receptor RXFP1 signals through a mechanism of autoinhibition. 著者: Sarah C Erlandson / Shaun Rawson / James Osei-Owusu / Kelly P Brock / Xinyue Liu / Joao A Paulo / Julian Mintseris / Steven P Gygi / Debora S Marks / Xiaojing Cong / Andrew C Kruse / ![]() ![]() 要旨: The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor ...The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and leucine-rich repeats. The mechanism of RXFP1 signal transduction is clearly distinct from that of other GPCRs, but remains very poorly understood. In the present study, we determine the cryo-electron microscopy structure of active-state human RXFP1, bound to a single-chain version of the endogenous agonist relaxin-2 and the heterotrimeric G protein. Evolutionary coupling analysis and structure-guided functional experiments reveal that RXFP1 signals through a mechanism of autoinhibition. Our results explain how an unusual GPCR family functions, providing a path to rational drug development targeting the relaxin receptors. #1: ![]() タイトル: The relaxin receptor RXFP1 signals through a mechanism of autoinhibition 著者: Erlandson SC / Rawson S / Osei-Owusu J / Brock KP / Liu X / Paulo JA / Mintseris J / Gygi SP / Marks DS / Cong X / Kruse AC | |||||||||
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 | ![]() | 68.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 31.9 KB 31.9 KB | 表示 表示 | ![]() |
画像 | ![]() | 43.5 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() ![]() | 80.8 MB 80.2 MB 81 MB 80.8 MB 84.5 MB 84.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 692.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 692.5 KB | 表示 | |
XML形式データ | ![]() | 13.3 KB | 表示 | |
CIF形式データ | ![]() | 15.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 7tmwMC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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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 | ![]() | ||||||||||||||||||||||||||||||||||||
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注釈 | Primary map used for model building, generated from a combine focused maps job in Phenix. | ||||||||||||||||||||||||||||||||||||
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: 1.06 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
-追加マップ: DeepEMhancer post-processed map generated after 3D focused classifications...
ファイル | emd_26003_additional_1.map | ||||||||||||
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注釈 | DeepEMhancer post-processed map generated after 3D focused classifications of transmembrane helix 1. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: DeepEMhancer post-processed map generated after 3D focused classifications...
ファイル | emd_26003_additional_2.map | ||||||||||||
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注釈 | DeepEMhancer post-processed map generated after 3D focused classifications of extracellular loops. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: DeepEMhancer post-processed map generated after 3D focused classifications...
ファイル | emd_26003_additional_3.map | ||||||||||||
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注釈 | DeepEMhancer post-processed map generated after 3D focused classifications of extracellular loops. | ||||||||||||
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密度ヒストグラム |
-追加マップ: DeepEMhancer post-processed map generated after 3D focused classifications...
ファイル | emd_26003_additional_4.map | ||||||||||||
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注釈 | DeepEMhancer post-processed map generated after 3D focused classifications of helix8. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half-map from cryoSPARC refinement for map J8.
ファイル | emd_26003_half_map_1.map | ||||||||||||
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注釈 | Half-map from cryoSPARC refinement for map J8. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half-map from cryoSPARC refinement for map J8.
ファイル | emd_26003_half_map_2.map | ||||||||||||
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注釈 | Half-map from cryoSPARC refinement for map J8. | ||||||||||||
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 : Complex of the relaxin receptor RXFP1 and heterotrimeric Gs
全体 | 名称: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs |
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要素 |
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-超分子 #1: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs
超分子 | 名称: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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分子量 | 理論値: 180 KDa |
-超分子 #2: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subun...
超分子 | 名称: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() |
-超分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,...
超分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #2-#3 |
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由来(天然) | 生物種: ![]() |
-超分子 #4: Camelid antibody VHH fragment Nb35
超分子 | 名称: Camelid antibody VHH fragment Nb35 / タイプ: complex / ID: 4 / 親要素: 1 / 含まれる分子: #4 |
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由来(天然) | 生物種: ![]() ![]() |
-分子 #1: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subun...
分子 | 名称: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion 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: ![]() |
分子量 | 理論値: 113.442891 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEA ETPECLVGSV PVQCLCQGLE LDCDETNLRA VPSVSSNVTA MSLQWNLIRK LPPDCFKNYH DLQKLYLQNN K ITSISIYA ...文字列: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEA ETPECLVGSV PVQCLCQGLE LDCDETNLRA VPSVSSNVTA MSLQWNLIRK LPPDCFKNYH DLQKLYLQNN K ITSISIYA FRGLNSLTKL YLSHNRITFL KPGVFEDLHR LEWLIIEDNH LSRISPPTFY GLNSLILLVL MNNVLTRLPD KP LCQHMPR LHWLDLEGNH IHNLRNLTFI SCSNLTVLVM RKNKINHLNE NTFAPLQKLD ELDLGSNKIE NLPPLIFKDL KEL SQLNLS YNPIQKIQAN QFDYLVKLKS LSLEGIEISN IQQRMFRPLM NLSHIYFKKF QYCGYAPHVR SCKPNTDGIS SLEN LLASI IQRVFVWVVS AVTCFGNIFV ICMRPYIRSE NKLYAMSIIS LCCADCLMGI YLFVIGGFDL KFRGEYNKHA QLWME STHC QLVGSLAILS TEVSVLLLTF LTLEKYICIV YPFRCVRPGK CRTITVLILI WITGFIVAFI PLSNKEFFKN YYGTNG VCF PLHSEDTESI GAQIYSVAIF LGINLAAFII IVFSYGSMFY SVHQSAITAT EIRNQVKKEM ILAKRFFFIV FTDALCW IP IFVVKFLSLL QVEIPGTITS WVVIFILPIN SALNPILYTL TTRPFKEMIH RFWYNYRQRK SMDSKGQKTY APSFIWVE M WPLQEMPPEL MKPDLNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHGGSGG SGGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRDEFLRIS TASGDGRHYC YPHFTCAVDT E NARRIFND CRDIIQRMHL RQYELL UniProtKB: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-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: 38.534062 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN 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: Camelid antibody VHH fragment Nb35
分子 | 名称: Camelid antibody VHH fragment Nb35 / 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: ![]() ![]() |
分子量 | 理論値: 17.444324 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSL EVLFQGPGHH HHHHHHGSED QVDPRLIDGK |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.2 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / メッシュ: 400 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 283.15 K / 装置: FEI VITROBOT MARK IV |
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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 BIOQUANTUM (6k x 4k) 平均電子線量: 52.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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): 2.3000000000000003 µm 最小 デフォーカス(公称値): 0.8 µm / 倍率(公称値): 81000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |