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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 calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation (repeat) | ||||||||||||||||||
マップデータ | |||||||||||||||||||
試料 |
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キーワード | Obesity / calcitonin receptor / amylin receptor / receptor activity-modifying protein / GPCR / MEMBRANE PROTEIN | ||||||||||||||||||
| 機能・相同性 | 機能・相同性情報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 ...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 / negative regulation of ossification / response to amyloid-beta / positive regulation of cAMP/PKA signal transduction / 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 / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / regulation of mRNA stability / cellular response to glucagon stimulus / acrosomal vesicle / regulation of insulin secretion / positive regulation of calcium-mediated signaling / ossification / response to glucocorticoid / osteoclast differentiation / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / bone development / platelet aggregation / G-protein beta/gamma-subunit complex binding / cognition / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine 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 / sensory perception of smell / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / 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 / 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 / Ca2+ pathway / fibroblast proliferation / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / Ras protein signal transduction / cell surface receptor signaling pathway / Extra-nuclear estrogen signaling 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: 3.4 Å | ||||||||||||||||||
データ登録者 | Cao J / Belousoff MJ / Johnson RM / 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_44905.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-44905-v30.xml emd-44905.xml | 37.6 KB 37.6 KB | 表示 表示 | EMDBヘッダ |
| FSC (解像度算出) | emd_44905_fsc.xml | 9.5 KB | 表示 | FSCデータファイル |
| 画像 | emd_44905.png | 36.1 KB | ||
| マスクデータ | emd_44905_msk_1.map | 91.1 MB | マスクマップ | |
| Filedesc metadata | emd-44905.cif.gz | 8.5 KB | ||
| その他 | emd_44905_additional_1.map.gz emd_44905_additional_2.map.gz emd_44905_additional_3.map.gz emd_44905_additional_4.map.gz emd_44905_half_map_1.map.gz emd_44905_half_map_2.map.gz | 84.7 MB 44 MB 84.7 MB 45.4 MB 84.7 MB 84.6 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-44905 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-44905 | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 9bucMC ![]() 9blbC ![]() 9blcC ![]() 9blwC ![]() 9bp3C ![]() 9bq3C ![]() 9btwC ![]() 9bubC ![]() 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_44905.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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| 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 | ||||||||||||||||||||||||||||||||||||
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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 | emd_44905_msk_1.map | ||||||||||||
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| 密度ヒストグラム |
-追加マップ: filtered map for the receptor region from the local refinement
| ファイル | emd_44905_additional_1.map | ||||||||||||
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| 注釈 | filtered map for the receptor region from the local refinement | ||||||||||||
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| 密度ヒストグラム |
-追加マップ: unfiltered map for the receptor region from the local refinement
| ファイル | emd_44905_additional_2.map | ||||||||||||
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| 注釈 | unfiltered map for the receptor region from the local refinement | ||||||||||||
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| 密度ヒストグラム |
-追加マップ: filtered map for the receptor region from the...
| ファイル | emd_44905_additional_3.map | ||||||||||||
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| 注釈 | filtered map for the receptor region from the local refinement using sub-group particles | ||||||||||||
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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_44905_additional_4.map | ||||||||||||
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| 注釈 | unfiltered consensus map | ||||||||||||
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| 密度ヒストグラム |
-ハーフマップ: #2
| ファイル | emd_44905_half_map_1.map | ||||||||||||
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_44905_half_map_2.map | ||||||||||||
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試料の構成要素
-全体 : Human calcitonin Receptor in complex with Gs and cagrilintide in ...
| 全体 | 名称: Human calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation (repeat) |
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| 要素 |
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-超分子 #1: Human calcitonin Receptor in complex with Gs and cagrilintide in ...
| 超分子 | 名称: Human calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation (repeat) タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #2-#6 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Cagrilintide
| 分子 | 名称: Cagrilintide / 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: 4.091543 KDa |
| 配列 | 文字列: (GGL)KCNTATCAT QRLAEFLRHS SNNFGPILPP TNVGSNTP |
-分子 #2: Calcitonin receptor
| 分子 | 名称: Calcitonin receptor / 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: 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 #3: 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: 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: 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 #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: 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 #5: 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: 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: 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 #6: Nanobody 35
| 分子 | 名称: Nanobody 35 / 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: 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 #7: icosanedioic acid
| 分子 | 名称: icosanedioic acid / タイプ: ligand / ID: 7 / コピー数: 1 / 式: A1B90 |
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| 分子量 | 理論値: 342.513 Da |
-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
| 濃度 | 4 mg/mL | ||||||||||||
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| 緩衝液 | pH: 7.4 構成要素:
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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 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
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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) 実像数: 4799 / 平均露光時間: 6.08 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 | 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): 1.2 µm / 最小 デフォーカス(公称値): 0.6 µm |
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

