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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 amylin1 Receptor in complex with Gs and Cagrilintide backbone (non-acylated) | ||||||||||||||||||
マップデータ | filtered map of consensus complex map | ||||||||||||||||||
試料 |
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キーワード | obesity / GPCR / calcitonin receptor / amylin receptor / receptor activity-modifying protein / MEMBRANE PROTEIN | ||||||||||||||||||
| 機能・相同性 | 機能・相同性情報calcitonin gene-related peptide binding / CGRP receptor complex / : / 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 gene-related peptide binding / CGRP receptor complex / : / 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 / calcitonin gene-related peptide receptor activity / amylin receptor 3 signaling pathway / amylin receptor 2 signaling pathway / amylin receptor 1 signaling pathway / amylin receptor signaling pathway / Calcitonin-like ligand receptors / regulation of G protein-coupled receptor signaling pathway / negative regulation of ossification / positive regulation of cAMP/PKA signal transduction / response to amyloid-beta / 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 / renal water homeostasis / activation of adenylate cyclase activity / cellular response to hormone stimulus / Hedgehog 'off' state / coreceptor activity / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mRNA stability / cellular response to glucagon stimulus / regulation of insulin secretion / acrosomal vesicle / positive regulation of calcium-mediated signaling / ossification / response to glucocorticoid / osteoclast differentiation / adenylate cyclase activator activity / trans-Golgi network membrane / protein localization to plasma membrane / intracellular protein transport / negative regulation of inflammatory response to antigenic stimulus / bone development / receptor internalization / G-protein beta/gamma-subunit complex binding / platelet aggregation / cognition / Olfactory Signaling Pathway / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / calcium ion transport / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / sensory perception of smell / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / protein transport / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / amyloid-beta binding / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding 類似検索 - 分子機能 | ||||||||||||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | ||||||||||||||||||
| 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 | ||||||||||||||||||
データ登録者 | Cao J / Belousoff MJ / Sexton PM / Wootten DL | ||||||||||||||||||
| 資金援助 | オーストラリア, 5件
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引用 | ジャーナル: Nat Commun / 年: 2025タイトル: Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. 著者: Jianjun Cao / Matthew J Belousoff / Rachel M Johnson / Peter Keov / Zamara Mariam / Giuseppe Deganutti / George Christopoulos / Caroline A Hick / Steffen Reedtz-Runge / Tine Glendorf / Borja ...著者: Jianjun Cao / Matthew J Belousoff / Rachel M Johnson / Peter Keov / Zamara Mariam / Giuseppe Deganutti / George Christopoulos / Caroline A Hick / Steffen Reedtz-Runge / Tine Glendorf / Borja Ballarín-González / Kirsten Raun / Charles Bayly-Jones / Denise Wootten / Patrick M Sexton / ![]() 要旨: Obesity is a major and increasingly prevalent chronic metabolic disease with numerous comorbidities. While recent incretin-based therapies have provided pharmaceutical inroads into treatment of ...Obesity is a major and increasingly prevalent chronic metabolic disease with numerous comorbidities. While recent incretin-based therapies have provided pharmaceutical inroads into treatment of obesity, there remains an ongoing need for additional medicines with distinct modes of action as independent or complementary therapeutics. Among the most promising candidates, supported by phase 1 and 2 clinical trials, is cagrilintide, a long-acting amylin and calcitonin receptor agonist. As such, understanding how cagrilintide functionally engages target receptors is critical for future development of this target class. Here, we determine structures of cagrilintide bound to Gs-coupled, active, amylin receptors (AMYR, AMYR, AMYR) and calcitonin receptor (CTR) and compare cagrilintide interactions and the dynamics of receptor complexes with previously reported structures of receptors bound to rat amylin, salmon calcitonin or recently developed amylin-based peptides. These data reveal that cagrilintide has an amylin-like binding mode but, compared to other peptides, induces distinct conformational dynamics at calcitonin-family receptors that could contribute to its clinical efficacy. | ||||||||||||||||||
| 履歴 |
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構造の表示
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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_44678.map.gz | 86 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-44678-v30.xml emd-44678.xml | 43.9 KB 43.9 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_44678_fsc.xml | 10.3 KB | 表示 | FSCデータファイル |
| 画像 | emd_44678.png | 35.5 KB | ||
| マスクデータ | emd_44678_msk_1.map | 91.1 MB | マスクマップ | |
| Filedesc metadata | emd-44678.cif.gz | 8.5 KB | ||
| その他 | emd_44678_additional_1.map.gz emd_44678_additional_2.map.gz emd_44678_additional_3.map.gz emd_44678_additional_4.map.gz emd_44678_additional_5.map.gz emd_44678_additional_6.map.gz emd_44678_additional_7.map.gz emd_44678_half_map_1.map.gz emd_44678_half_map_2.map.gz | 45.7 MB 85 MB 44.3 MB 83.5 MB 44.2 MB 84.5 MB 44.2 MB 84.5 MB 84.6 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-44678 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44678 | HTTPS FTP |
-検証レポート
| 文書・要旨 | emd_44678_validation.pdf.gz | 951 KB | 表示 | EMDB検証レポート |
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| 文書・詳細版 | emd_44678_full_validation.pdf.gz | 950.5 KB | 表示 | |
| XML形式データ | emd_44678_validation.xml.gz | 17.5 KB | 表示 | |
| CIF形式データ | emd_44678_validation.cif.gz | 22.8 KB | 表示 | |
| アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44678 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-44678 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9blwMC ![]() 9blbC ![]() 9blcC ![]() 9bp3C ![]() 9bq3C ![]() 9btwC ![]() 9bubC ![]() 9bucC ![]() 9budC ![]() 9bueC 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 F&H 検索 |
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_44678.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 | filtered map of consensus complex 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: 0.86 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
+追加マップ: unfiltered consensus map for the complex
+追加マップ: filtered map of receptor-focused refinement
+追加マップ: unfiltered map of receptor-focused refinement
+追加マップ: filtered map of receptor-focused refinement from more amount...
+追加マップ: unfiltered map of receptor-focused refinement from more amount...
+追加マップ: filtered map of consensus complex map from more...
+追加マップ: unfiltered map of consensus complex map from more...
+ハーフマップ: #1
+ハーフマップ: #2
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試料の構成要素
-全体 : Human amylin1 Receptor in complex with Gs and Cagrilintide backbo...
| 全体 | 名称: Human amylin1 Receptor in complex with Gs and Cagrilintide backbone (non-acylated) |
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| 要素 |
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-超分子 #1: Human amylin1 Receptor in complex with Gs and Cagrilintide backbo...
| 超分子 | 名称: Human amylin1 Receptor in complex with Gs and Cagrilintide backbone (non-acylated) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5, #7 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-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: 45.699434 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 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 38.534062 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 7.861143 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 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 1
| 分子 | 名称: Receptor activity-modifying protein 1 / 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: 17.066701 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 DDDKHGSCQE ANYGALLREL CLTQFQVDME AVGETLWCDW GRTIRSYREL ADCTWHMAEK LGCFWPNAE VDRFFLAVHG RYFRSCPISG RAVRDPPGSI LYPFIVVPIT VTLLVTALVV WQSKRTEGIV UniProtKB: Receptor activity-modifying protein 1 |
-分子 #6: Cagrilintide backbone (non-acylated)
| 分子 | 名称: Cagrilintide backbone (non-acylated) / 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 3.960437 KDa |
| 配列 | 文字列: KCNTATCATQ RLAEFLRHSS NNFGPILPPT NVGSNTP(NH2) |
-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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 53.796309 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: GPAAFSNQTY PTIEPKPFLY VVGRKKMMDA QYKCYDRMQQ LPAYQGEGPY CNRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTK YCDEKGVWFK HPENNRTWSN YTMCNAFTPE KLKNAYVLYY LAIVGHSLSI FTLVISLGIF VFFRSLGCQR V TLHKNMFL ...文字列: GPAAFSNQTY PTIEPKPFLY VVGRKKMMDA QYKCYDRMQQ LPAYQGEGPY CNRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTK YCDEKGVWFK HPENNRTWSN YTMCNAFTPE KLKNAYVLYY LAIVGHSLSI FTLVISLGIF VFFRSLGCQR V TLHKNMFL TYILNSMIII IHLVEVVPNG ELVRRDPVSC KILHFFHQYM MACNYFWMLC EGIYLHTLIV VAVFTEKQRL RW YYLLGWG FPLVPTTIHA ITRAVYFNDN CWLSVETHLL YIIHGPVMAA LVVNFFFLLN IVRVLVTKMR ETHEAESHMY LKA VKATMI LVPLLGIQFV VFPWRPSNKM LGKIYDYVMH SLIHFQGFFV ATIYCFCNNE VQTTVKRQWA QFKIQWNQRW GRRP SNRSA RAAAAAAEAG DIPIYICHQE LRNEPANNQG EESAEIIPLN IIEQESSAPA GLEVLFQ UniProtKB: Calcitonin receptor |
-分子 #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
| 分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 8 / コピー数: 1 / 式: NAG |
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| 分子量 | 理論値: 221.208 Da |
| Chemical component information | ![]() ChemComp-NAG: |
-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 |
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試料調製
| 緩衝液 | pH: 7.4 |
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| グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 120 sec. |
| 凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % |
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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) 平均露光時間: 7.91 sec. / 平均電子線量: 50.0 e/Å2 |
| 電子線 | 加速電圧: 200 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 FIELD / 最大 デフォーカス(公称値): 1.1 µm / 最小 デフォーカス(公称値): 0.6 µm |
| 試料ステージ | ホルダー冷却材: NITROGEN |
ムービー
コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
オーストラリア, 5件
引用







































Z (Sec.)
Y (Row.)
X (Col.)




































































































Trichoplusia ni (イラクサキンウワバ)

解析
FIELD EMISSION GUN

