+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-8623 | |||||||||
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タイトル | Volta phase plate cryo-electron microscopy structure of a calcitonin receptor-heterotrimeric Gs protein complex | |||||||||
マップデータ | ||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / positive regulation of adenylate cyclase activity ...calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / positive regulation of adenylate cyclase activity / Calcitonin-like ligand receptors / negative regulation of ossification / positive regulation of protein kinase A signaling / PKA activation in glucagon signalling / response to amyloid-beta / intracellular transport / hair follicle placode formation / D1 dopamine receptor binding / developmental growth / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / positive regulation of calcium-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / regulation of mRNA stability / activation of adenylate cyclase activity / adenylate cyclase activator activity / 骨化 / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / 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 / 骨 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / 繊毛 / G beta:gamma signalling through CDC42 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 認識 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / 血小板 / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / positive regulation of GTPase activity / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / cellular response to prostaglandin E stimulus / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / sensory perception of smell / 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 / amyloid-beta binding / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / G protein-coupled receptor signaling pathway / lysosomal membrane / 神経繊維 / GTPase activity / シナプス / protein-containing complex binding 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: 4.1 Å | |||||||||
データ登録者 | Liang YL / Khoshouei M / Radjainia M / Zhang Y / Glukhova A / Tarrasch J / Thal DM / Furness SGB / Christopoulos G / Coudrat T ...Liang YL / Khoshouei M / Radjainia M / Zhang Y / Glukhova A / Tarrasch J / Thal DM / Furness SGB / Christopoulos G / Coudrat T / Danev R / Baumeister W / Miller LJ / Christopoulos A / Kobilka BK / Wootten D / Skiniotis G / Sexton PM | |||||||||
引用 | ジャーナル: Nature / 年: 2017 タイトル: Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. 著者: Yi-Lynn Liang / Maryam Khoshouei / Mazdak Radjainia / Yan Zhang / Alisa Glukhova / Jeffrey Tarrasch / David M Thal / Sebastian G B Furness / George Christopoulos / Thomas Coudrat / Radostin ...著者: Yi-Lynn Liang / Maryam Khoshouei / Mazdak Radjainia / Yan Zhang / Alisa Glukhova / Jeffrey Tarrasch / David M Thal / Sebastian G B Furness / George Christopoulos / Thomas Coudrat / Radostin Danev / Wolfgang Baumeister / Laurence J Miller / Arthur Christopoulos / Brian K Kobilka / Denise Wootten / Georgios Skiniotis / Patrick M Sexton / 要旨: Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B ...Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calcitonin receptor, in complex with peptide ligand and heterotrimeric Gαβγ protein determined by Volta phase-plate single-particle cryo-electron microscopy. The peptide agonist engages the receptor by binding to an extended hydrophobic pocket facilitated by the large outward movement of the extracellular ends of transmembrane helices 6 and 7. This conformation is accompanied by a 60° kink in helix 6 and a large outward movement of the intracellular end of this helix, opening the bundle to accommodate interactions with the α5-helix of Gα. Also observed is an extended intracellular helix 8 that contributes to both receptor stability and functional G-protein coupling via an interaction with the Gβ subunit. This structure provides a new framework for understanding G-protein-coupled receptor function. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_8623.map.gz | 28.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-8623-v30.xml emd-8623.xml | 16.6 KB 16.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_8623.png | 122.1 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-8623 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-8623 | HTTPS FTP |
-関連構造データ
-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_8623.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Complex of a full-length, active-state calcitonin receptor with p...
全体 | 名称: Complex of a full-length, active-state calcitonin receptor with peptide ligand, heterotrimeric Gs protein and nano body 35. |
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要素 |
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-超分子 #1: Complex of a full-length, active-state calcitonin receptor with p...
超分子 | 名称: Complex of a full-length, active-state calcitonin receptor with peptide ligand, heterotrimeric Gs protein and nano body 35. 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) |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
分子量 | 理論値: 150 KDa |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 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: 44.32616 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM RILHVNGFNG DSEKATKVQD IKNNLKEAI ETIVAAMSNL VPPVELANPE NQFRVDYILS VMNVPDFDFP PEFYEHAKAL WEDEGVRACY ERSNEYQLID C AQYFLDKI DVIKQADYVP SDQDLLRCRV LTSGIFETKF QVDKVNFHMF DVGGQRDERR KWIQCFNDVT AIIFVVASSS YN MVIREDN QTNRLQEALN LFKSIWNNRW LRTISVILFL NKQDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED PRV TRAKYF IRDEFLRIST ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 38.744371 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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 |
-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: Homo sapiens (ヒト) |
分子量 | 理論値: 7.56375 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFC |
-分子 #4: NANOBODY 35
分子 | 名称: NANOBODY 35 / 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: Lama Glama (ラマ) |
分子量 | 理論値: 15.140742 KDa |
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 LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #5: Calcitonin receptor
分子 | 名称: Calcitonin receptor / 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: 58.469594 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI ...文字列: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI FTLVISLGIF VFFRSLGCQR VTLHKNMFLT YILNSMIIII HLVEVVPNGE LVRRDPVSCK ILHFFHQYMM AC NYFWMLC EGIYLHTLIV VAVFTEKQRL RWYYLLGWGF PLVPTTIHAI TRAVYFNDNC WLSVETHLLY IIHGPVMAAL VVN FFFLLN IVRVLVTKMR ETHEAESHMY LKAVKATMIL VPLLGIQFVV FPWRPSNKML GKIYDYVMHS LIHFQGFFVA TIYC FCNNE VQTTVKRQWA QFKIQWNQRW GRRPSNRSAR AAAAAAEAGD IPIYICHQEL RNEPANNQGE ESAEIIPLNI IEQES SAPA GLEVLFQGPH HHHHHHH |
-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 | 0.3 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: 300 / 前処理 - タイプ: GLOW DISCHARGE |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 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 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELDBright-field microscopy |
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 K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 50.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: PROJECTION MATCHING |
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最終 角度割当 | タイプ: PROJECTION MATCHING |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 106838 |