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- EMDB-26179: Human Amylin2 Receptor in complex with Gs and human calcitonin peptide -
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データを開く
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基本情報
登録情報 | ![]() | ||||||||||||||||||||||||
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タイトル | Human Amylin2 Receptor in complex with Gs and human calcitonin peptide | ||||||||||||||||||||||||
![]() | post-processed consensus map | ||||||||||||||||||||||||
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![]() | Amylin receptor / GPCR / RAMP2 / human calcitonin / MEMBRANE PROTEIN | ||||||||||||||||||||||||
機能・相同性 | ![]() calcitonin receptor binding / basement membrane assembly / adrenomedullin binding / adrenomedullin receptor activity / adrenomedullin receptor complex / vascular associated smooth muscle cell development / adrenomedullin receptor signaling pathway / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 ...calcitonin receptor binding / basement membrane assembly / adrenomedullin binding / adrenomedullin receptor activity / adrenomedullin receptor complex / vascular associated smooth muscle cell development / adrenomedullin receptor signaling pathway / calcitonin binding / calcitonin family receptor activity / amylin receptor complex 1 / amylin receptor complex 2 / calcitonin family receptor signaling pathway / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor signaling pathway / activation of protein kinase activity / calcitonin gene-related peptide receptor activity / amylin receptor 3 signaling pathway / amylin receptor 2 signaling pathway / positive regulation of vasculogenesis / bicellular tight junction assembly / amylin receptor 1 signaling pathway / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / negative regulation of vascular permeability / adherens junction assembly / negative regulation of smooth muscle contraction / sprouting angiogenesis / negative regulation of ossification / negative regulation of bone resorption / monocyte chemotaxis / response to amyloid-beta / positive regulation of cAMP/PKA signal transduction / PKA activation in glucagon signalling / developmental growth / cellular response to vascular endothelial growth factor stimulus / hair follicle placode formation / regulation of cytosolic calcium ion concentration / D1 dopamine receptor binding / neuronal dense core vesicle / intracellular transport / negative regulation of endothelial cell apoptotic process / vascular endothelial cell response to laminar fluid shear stress / vasculogenesis / activation of adenylate cyclase activity / renal water homeostasis / cellular response to hormone stimulus / Hedgehog 'off' state / coreceptor activity / negative regulation of blood pressure / adenylate cyclase-activating adrenergic receptor signaling pathway / clathrin-coated pit / regulation of mRNA stability / embryo implantation / cellular response to glucagon stimulus / regulation of insulin secretion / acrosomal vesicle / positive regulation of calcium-mediated signaling / ossification / response to glucocorticoid / osteoclast differentiation / hippocampal mossy fiber to CA3 synapse / adenylate cyclase activator activity / trans-Golgi network membrane / protein localization to plasma membrane / intracellular protein transport / negative regulation of inflammatory response to antigenic stimulus / hormone activity / bone development / cellular response to nerve growth factor stimulus / receptor internalization / regulation of blood pressure / platelet aggregation / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / vasodilation / 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 / positive regulation of angiogenesis / 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 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: 3.3 Å | ||||||||||||||||||||||||
![]() | Cao J / Belousoff MJ | ||||||||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: A structural basis for amylin receptor phenotype. 著者: Jianjun Cao / Matthew J Belousoff / Yi-Lynn Liang / Rachel M Johnson / Tracy M Josephs / Madeleine M Fletcher / Arthur Christopoulos / Debbie L Hay / Radostin Danev / Denise Wootten / Patrick M Sexton / ![]() ![]() ![]() 要旨: Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual ...Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMYR with salmon CT (sCT), AMYR with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics. | ||||||||||||||||||||||||
履歴 |
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 95.8 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 34.6 KB 34.6 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 10.7 KB | 表示 | ![]() |
画像 | ![]() | 28 KB | ||
マスクデータ | ![]() | 103 MB | ![]() | |
Filedesc metadata | ![]() | 8 KB | ||
その他 | ![]() ![]() ![]() ![]() ![]() | 81.1 MB 93.5 MB 91.8 MB 81.4 MB 81.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 17.7 KB | 表示 | |
CIF形式データ | ![]() | 23.4 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 | ![]() 7tyhMC ![]() 7tyfC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 7tyxC ![]() 7tyyC ![]() 7tzfC 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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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
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注釈 | post-processed consensus map | ||||||||||||||||||||||||||||||||||||
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: 0.856 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
-マスク #1
ファイル | ![]() | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: unfiltered consensus map
ファイル | emd_26179_additional_1.map | ||||||||||||
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注釈 | unfiltered consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: a post-processed map that focused on receptor region...
ファイル | emd_26179_additional_2.map | ||||||||||||
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注釈 | a post-processed map that focused on receptor region and was resampled to the consensus map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: an unfiltered map that focused on receptor region...
ファイル | emd_26179_additional_3.map | ||||||||||||
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注釈 | an unfiltered map that focused on receptor region and was resampled to the consensus map | ||||||||||||
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 for the consensus map refinement
ファイル | emd_26179_half_map_1.map | ||||||||||||
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注釈 | half map for the consensus map refinement | ||||||||||||
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 for the consensus map refinement
ファイル | emd_26179_half_map_2.map | ||||||||||||
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注釈 | half map for the consensus map refinement | ||||||||||||
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 : Human Amylin 2 Receptor in complex with Gs and human calcitonin p...
全体 | 名称: Human Amylin 2 Receptor in complex with Gs and human calcitonin peptide |
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要素 |
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-超分子 #1: Human Amylin 2 Receptor in complex with Gs and human calcitonin p...
超分子 | 名称: Human Amylin 2 Receptor in complex with Gs and human calcitonin peptide タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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-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: ![]() |
分子量 | 理論値: 45.699434 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...文字列: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCS VDTENIRRVF NDCRDIIQRM HLRQYELL UniProtKB: 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: 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: ![]() ![]() |
分子量 | 理論値: 15.140742 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 QGTQVTVSSH HHHHHEPEA |
-分子 #5: Receptor activity-modifying protein 2
分子 | 名称: Receptor activity-modifying protein 2 / 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: 17.839375 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKPLPTTG TPGSEGGTVK NYETAVQFCW NHYKDQMDPI EKDWCDWAMI SRPYSTLRDC LEHFAELFD LGFPNPLAER IIFETHQIHF ANCSLVQPTF SDPPEDVLLA MIIAPICLIP FLITLVVWRS KDSEAQA UniProtKB: Receptor activity-modifying protein 2 |
-分子 #6: Calcitonin
分子 | 名称: Calcitonin / 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: ![]() |
分子量 | 理論値: 3.42087 KDa |
配列 | 文字列: CGNLSTCMLG TYTQDFNKFH TFPQTAIGVG AP(NH2) UniProtKB: Calcitonin |
-分子 #7: Calcitonin receptor
分子 | 名称: Calcitonin receptor / 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: ![]() |
分子量 | 理論値: 58.469594 KDa |
組換発現 | 生物種: ![]() |
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 UniProtKB: Calcitonin receptor |
-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 | 4 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | TFS GLACIOS |
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撮影 | フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 200 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): 1.5 µm / 最小 デフォーカス(公称値): 0.5 µm |