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基本情報
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タイトル | Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein | ||||||||||||||||||
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![]() | GPCR / corticotropin releasing factor receptor 2 / Urocortin 1 / G11 protein / SIGNALING PROTEIN | ||||||||||||||||||
機能・相同性 | ![]() histone deacetylase inhibitor activity / corticotropin-releasing hormone receptor activity / regulation of melanocyte differentiation / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / positive regulation of corticotropin secretion / positive regulation of behavioral fear response / varicosity / : / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway ...histone deacetylase inhibitor activity / corticotropin-releasing hormone receptor activity / regulation of melanocyte differentiation / corticotrophin-releasing factor receptor activity / corticotropin-releasing hormone receptor 2 binding / positive regulation of corticotropin secretion / positive regulation of behavioral fear response / varicosity / : / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / negative regulation of hormone secretion / Acetylcholine regulates insulin secretion / endothelin receptor signaling pathway / phospholipase C-activating dopamine receptor signaling pathway / developmental pigmentation / response to auditory stimulus / drinking behavior / PLC beta mediated events / cranial skeletal system development / cellular response to pH / negative regulation of appetite / entrainment of circadian clock / corticotropin-releasing hormone receptor 1 binding / neuropeptide hormone activity / negative regulation of cell size / 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 vascular permeability / 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 / Class B/2 (Secretin family receptors) / G protein-coupled peptide receptor activity / 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) / photoreceptor outer segment membrane / response to pain / spectrin binding / negative regulation of feeding behavior / positive regulation of calcium ion import / startle response / alkylglycerophosphoethanolamine phosphodiesterase activity / ligand-gated ion channel signaling pathway / social behavior / associative learning / positive regulation of cAMP/PKA signal transduction / peptide hormone binding / action potential / phototransduction, visible light / positive regulation of collagen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / photoreceptor outer segment / neuropeptide signaling pathway / response to glucocorticoid / regulation of synaptic transmission, glutamatergic / enzyme regulator activity / negative regulation of blood pressure / axon terminus / photoreceptor inner segment / cardiac muscle cell apoptotic process / positive regulation of cardiac muscle contraction / aerobic respiration / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / positive regulation of translation / positive regulation of DNA replication / skeletal system development / female pregnancy / sensory perception of sound / G protein-coupled receptor binding / positive regulation of insulin secretion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of blood pressure / positive regulation of interleukin-6 production / G-protein beta/gamma-subunit complex binding / long-term synaptic potentiation / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / neuron projection development / vasodilation / ADP signalling through P2Y purinoceptor 1 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / heterotrimeric G-protein complex / sensory perception of taste / response to estradiol / signaling receptor complex adaptor activity 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: 3.7 Å | ||||||||||||||||||
![]() | Zhao L-H / Lin J / Mao C / Zhou XE / Ji S / Shen D / Xiao P / Melcher K / Zhang Y / Yu X / Xu HE | ||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor. 著者: Li-Hua Zhao / Jingyu Lin / Su-Yu Ji / X Edward Zhou / Chunyou Mao / Dan-Dan Shen / Xinheng He / Peng Xiao / Jinpeng Sun / Karsten Melcher / Yan Zhang / Xiao Yu / H Eric Xu / ![]() ![]() 要旨: The ability to couple with multiple G protein subtypes, such as G, G, or G, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the ...The ability to couple with multiple G protein subtypes, such as G, G, or G, by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G protein, have been determined. However, no structure of class B GPCRs with G has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G and G. We compare these structures with the structure of CRF2R in complex with G to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes. | ||||||||||||||||||
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マップデータ | ![]() | 40.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 20.5 KB 20.5 KB | 表示 表示 | ![]() |
画像 | ![]() | 78.5 KB | ||
Filedesc metadata | ![]() | 7.4 KB | ||
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 | ![]() 7tryMC ![]() 7ts0C C: 同じ文献を引用 ( M: このマップから作成された原子モデル |
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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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ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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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: 1.045 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
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試料の構成要素
-全体 : Corticotropin releasing factor receptor 2 (CRF2R) bound to Urocor...
全体 | 名称: Corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1) and coupled with G11 proteins |
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要素 |
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-超分子 #1: Corticotropin releasing factor receptor 2 (CRF2R) bound to Urocor...
超分子 | 名称: Corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1) and coupled with G11 proteins 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: ![]() |
-分子 #1: Corticotropin-releasing factor receptor 2
分子 | 名称: Corticotropin-releasing factor receptor 2 / 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: 63.716246 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DAALLHSLLE ANCSLALAEE LLLDGWGPPL DPEGPYSYCN TTLDQIGTCW PRSAAGALVE RPCPEYFNGV KYNTTRNAYR ECLENGTWA SKINYSQCEP ILDDKQRKYD LHYRIALVVN YLGHCVSVAA LVAAFLLFLA LRSIRCLRNV IHWNLITTFI L RNVMWFLL ...文字列: DAALLHSLLE ANCSLALAEE LLLDGWGPPL DPEGPYSYCN TTLDQIGTCW PRSAAGALVE RPCPEYFNGV KYNTTRNAYR ECLENGTWA SKINYSQCEP ILDDKQRKYD LHYRIALVVN YLGHCVSVAA LVAAFLLFLA LRSIRCLRNV IHWNLITTFI L RNVMWFLL QLVDHEVHES NEVWCRCITT IFNYFVVTNF FWMFVEGCYL HTAIVMTYST ERLRKCLFLF IGWCIPFPII VA WAIGKLY YENEQCWFGK EPGDLVDYIY QGPIILVLLI NFVFLFNIVR ILMTKLRAST TSETIQYRKA VKATLVLLPL LGI TYMLFF VNPGEDDLSQ IMFIYFNSFL QSFQGFFVSV FYCFFNGEVR SAVRKRWHRW QDHHSLRVPM AGSSGGGGSG GGGS SGVFT LEDFVGDWEQ TAAYNLDQVL EQGGVSSLLQ NLAVSVTPIQ RIVRSGENAL KIDIHVIIPY EGLSADQMAQ IEEVF KVVY PVDDHHFKVI LPYGTLVIDG VTPNMLNYFG RPYEGIAVFD GKKITVTGTL WNGNKIIDER LITPDGSMLF RVTINS UniProtKB: Corticotropin-releasing factor receptor 2 |
-分子 #2: Urocortin
分子 | 名称: Urocortin / 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: 4.703277 KDa |
配列 | 文字列: DNPSLSIDLT FHLLRTLLEL ARTQSQRERA EQNRIIFDSV UniProtKB: Urocortin |
-分子 #3: Guanine nucleotide-binding protein subunit alpha-11
分子 | 名称: Guanine nucleotide-binding protein subunit alpha-11 / 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: 41.415348 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLRRDKRDA RRELKLLLLG TGESGKSTFI KQMRIIHGAG YSEEDKRGFT KLVYQNIFTA MQAMIRAME TLKILYKYEQ NKANALLIRE VDVEKVTTFE HQYVSAIKTL WEDPGIQECY DRRREYQLSD SAKYYLTDVD R IATLGYLP ...文字列: MGCTLSAEDK AAVERSKMIE KQLRRDKRDA RRELKLLLLG TGESGKSTFI KQMRIIHGAG YSEEDKRGFT KLVYQNIFTA MQAMIRAME TLKILYKYEQ NKANALLIRE VDVEKVTTFE HQYVSAIKTL WEDPGIQECY DRRREYQLSD SAKYYLTDVD R IATLGYLP TQQDVLRVRV PTTGIIEYPF DLENIIFRMV DVGAQRSERR KWIHCFENVT SIMFLVALSE YDQVLVESDN EN RMEESKA LFRTIITYPW FQNSSVILFL NKKDLLEDKI LYSHLVDYFP EFDGPQRDAQ AAREFILKMF VDLNPDSDKI IYS HFTCST DTENIRFVFA AVKDTILQLN LKEYNLV UniProtKB: Guanine nucleotide-binding protein subunit alpha-11 |
-分子 #4: 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: 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: 43.70675 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHSSG LVPRGSHMAS HHHHHHHHHH GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN L KTREGNVR ...文字列: MHHHHHHSSG LVPRGSHMAS HHHHHHHHHH GSLLQSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN L KTREGNVR VSRELAGHTG YLSCCRFLDD NQIVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DA SAKLWDV REGMCRQTFT GHESDINAIC FFPNGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLL AGYDDF NCNVWDALKA DRAGVLAGHD NRVSCLGVTD DGMAVATGSW DSFLKIWNGS SGGGGSGGGG SSGVSGWRLF KKIS UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #5: G protein gamma subunit
分子 | 名称: G protein gamma subunit / 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: ![]() ![]() |
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 |
-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: 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 |
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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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 K2 SUMMIT (4k x 4k) 平均電子線量: 64.0 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): 4.0 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 |