EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors.
ジャーナル・号・ページ	Nat Commun, Vol. 16, Issue 1, Page 3389, Year 2025
掲載日	2025年4月10日
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 /
PubMed 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.
リンク	Nat Commun / PubMed:40204768 / PubMed Central
手法	EM (単粒子)
解像度	2.2 - 3.6 Å
構造データ	44652 9blb EMDB-44652, PDB-9blb: Human Calcitonin Receptor in Complex with Gs and Cagrilintide Backbone (non-acylated) in bypass conformation 手法: EM (単粒子) / 解像度: 3.2 Å 44653 9blc EMDB-44653, PDB-9blc: Human Calcitonin Receptor in Complex with Gs and Cagrilintide Backbone (non-acylated) in CT-like conformation 手法: EM (単粒子) / 解像度: 3.3 Å 44678 9blw EMDB-44678, PDB-9blw: Human amylin1 Receptor in complex with Gs and Cagrilintide backbone (non-acylated) 手法: EM (単粒子) / 解像度: 3.2 Å 44760 9bp3 EMDB-44760, PDB-9bp3: Human Amylin1 Receptor in complex with Gs and cagrilintide 手法: EM (単粒子) / 解像度: 2.2 Å 44796 9bq3 EMDB-44796, PDB-9bq3: Human Amylin2 Receptor in Complex with Gs and Cagrilintide 手法: EM (単粒子) / 解像度: 2.8 Å 44898 9btw EMDB-44898, PDB-9btw: Human Amylin3 Receptor in complex with Gs and cagrilintide 手法: EM (単粒子) / 解像度: 3.0 Å 44904 9bub EMDB-44904, PDB-9bub: Human calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation 手法: EM (単粒子) / 解像度: 2.3 Å 44905 9buc EMDB-44905, PDB-9buc: Human calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation (repeat) 手法: EM (単粒子) / 解像度: 3.4 Å 44906 9bud EMDB-44906, PDB-9bud: Human calcitonin Receptor in complex with Gs and cagrilintide in the CT-like conformation 手法: EM (単粒子) / 解像度: 2.5 Å 44907 9bue EMDB-44907, PDB-9bue: Human calcitonin Receptor in complex with Gs and cagrilintide in the CT-like conformation (repeat) 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose PDB-1b90: BACILLUS CEREUS BETA-AMYLASE APO FORM ChemComp-P42: (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl]oxy}propyl 2-(trimethylammonio)ethyl phosphate / SPPC, リン脂質YM ChemComp-Y01: CHOLESTEROL HEMISUCCINATE ChemComp-HOH*: WATER
由来	homo sapiens (ヒト) lama glama (ラマ)
キーワード	MEMBRANE PROTEIN / Amylin receptor / GPCR / RAMPs / Calcitonin receptor / Cagrilintide / obesity / receptor activity-modifying protein / RAMP2