+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26004 | |||||||||
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タイトル | Cryo-EM map of the full-length relaxin receptor RXFP1 in complex with heterotrimeric Gs | |||||||||
マップデータ | Relaxin receptor RXFP1 in complex with heterotrimeric Gs | |||||||||
試料 |
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キーワード | GPCR (Gタンパク質共役受容体) / Complex / Signaling / Relaxin (リラキシン) / MEMBRANE PROTEIN (膜タンパク質) | |||||||||
機能・相同性 | 機能・相同性情報 lung connective tissue development / nipple morphogenesis / Relaxin receptors / 出産 / myofibroblast differentiation / hormone binding / G protein-coupled peptide receptor activity / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth ...lung connective tissue development / nipple morphogenesis / Relaxin receptors / 出産 / myofibroblast differentiation / hormone binding / G protein-coupled peptide receptor activity / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / hormone-mediated signaling pathway / extracellular matrix organization / trans-Golgi network membrane / G protein-coupled receptor activity / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / 骨 / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / photoreceptor disc membrane / 認識 / 血小板 / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / positive regulation of GTPase activity / 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 / 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 / sensory perception of taste / GPER1 signaling / 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 / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cold-induced thermogenesis / 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 / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / シナプス / protein-containing complex binding / GTP binding / シグナル伝達 / extracellular exosome / 生体膜 / metal ion binding / 細胞膜 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Lama glama (ラマ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.2 Å | |||||||||
データ登録者 | Erlandson SC / Rawson S / Kruse AC | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nat Chem Biol / 年: 2023 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. | |||||||||
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_26004.map.gz | 55.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26004-v30.xml emd-26004.xml | 23.3 KB 23.3 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_26004.png | 35.3 KB | ||
その他 | emd_26004_additional_1.map.gz emd_26004_half_map_1.map.gz emd_26004_half_map_2.map.gz | 71.3 MB 71.4 MB 71.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26004 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26004 | HTTPS FTP |
-関連構造データ
関連構造データ | 7tmwC 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_26004.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Relaxin receptor RXFP1 in complex with heterotrimeric Gs | ||||||||||||||||||||
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: Relaxin receptor RXFP1 in complex with heterotrimeric Gs
ファイル | emd_26004_additional_1.map | ||||||||||||
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注釈 | Relaxin receptor RXFP1 in complex with heterotrimeric Gs | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Relaxin receptor RXFP1 in complex with heterotrimeric Gs
ファイル | emd_26004_half_map_1.map | ||||||||||||
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注釈 | Relaxin receptor RXFP1 in complex with heterotrimeric Gs | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Relaxin receptor RXFP1 in complex with heterotrimeric Gs
ファイル | emd_26004_half_map_2.map | ||||||||||||
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注釈 | Relaxin receptor RXFP1 in complex with heterotrimeric Gs | ||||||||||||
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 : 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 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: Homo sapiens (ヒト) |
-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: Homo sapiens (ヒト) |
-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: Lama glama (ラマ) |
-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 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEAE TPECLVGSVP VQCLCQGLEL DCDETNLRAV PSVSSNVTAM SLQWNLIRKL PPDCFKNYHD LQKLYLQNNK ITSISIYAFR ...文字列: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEAE TPECLVGSVP VQCLCQGLEL DCDETNLRAV PSVSSNVTAM SLQWNLIRKL PPDCFKNYHD LQKLYLQNNK ITSISIYAFR GLNSLTKLYL SHNRITFLKP GVFEDLHRLE WLIIEDNHLS RISPPTFYGL NSLILLVLMN NVLTRLPDKP LCQHMPRLHW LDLEGNHIHN LRNLTFISCS NLTVLVMRKN KINHLNENTF APLQKLDELD LGSNKIENLP PLIFKDLKEL SQLNLSYNPI QKIQANQFDY LVKLKSLSLE GIEISNIQQR MFRPLMNLSH IYFKKFQYCG YAPHVRSCKP NTDGISSLEN LLASIIQRVF VWVVSAVTCF GNIFVICMRP YIRSENKLYA MSIISLCCAD CLMGIYLFVI GGFDLKFRGE YNKHAQLWME STHCQLVGSL AILSTEVSVL LLTFLTLEKY ICIVYPFRCV RPGKCRTITV LILIWITGFI VAFIPLSNKE FFKNYYGTNG VCFPLHSEDT ESIGAQIYSV AIFLGINLAA FIIIVFSYGS MFYSVHQSAI TATEIRNQVK KEMILAKRFF FIVFTDALCW IPIFVVKFLS LLQVEIPGTI TSWVVIFILP INSALNPILY TLTTRPFKEM IHRFWYNYRQ RKSMDSKGQK TYAPSFIWVE MWPLQEMPPE LMKPDLNSKT EDQRNEEKAQ REANKKIEKQ LQKDKQVYRA THRLLLLGAD NSGKSTIVKQ MRIYHGGSGG SGGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST ASGDGRHYCY PHFTCAVDTE NARRIFNDCR DIIQRMHLRQ YELL 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 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TFTGHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KADRAGVLAG HDNRVSCLGV TDDGMAVATG SWDSFLKIWN 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 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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 / 光学異性体: LEVO |
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由来(天然) | 生物種: Lama glama (ラマ) |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPED TAVYYCARCP APFTRDCFDV TSTTYAYRGQ GTQVTVSSLE VLFQGPGHHH HHHHHGSEDQ VDPRLIDGK |
-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
濃度 | 0.2 mg/mL |
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緩衝液 | pH: 7.5 |
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 |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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 FIELDBright-field microscopy 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 |
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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
粒子像選択 | 選択した数: 15826542 |
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初期モデル | モデルのタイプ: OTHER / 詳細: Ab initio model generated in RELION |
初期 角度割当 | タイプ: RANDOM ASSIGNMENT / ソフトウェア - 名称: RELION (ver. 3.1) |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION (ver. 3.1) |
最終 再構成 | 想定した対称性 - 点群: C1 (非対称) / 解像度のタイプ: BY AUTHOR / 解像度: 4.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3.1) / 使用した粒子像数: 45146 |