9BLC

Human Calcitonin Receptor in Complex with Gs and Cagrilintide Backbone (non-acylated) in CT-like conformation

9BLC の概要

• エントリーDOI: 10.2210/pdb9blc/pdb
• 関連するPDBエントリー: 9BLB
• EMDBエントリー: 44653
• 分子名称: Cagrilintide backbone (non-acylated), Calcitonin receptor, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• 機能のキーワード: amylin receptor, gpcr, ramps, calcitonin receptor, cagrilintide, obesity, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 164992.13

構造登録者

Cao, J.,Belousoff, M.J.,Wootten, D.L.,Sexton, P.M. (登録日: 2024-04-30, 公開日: 2025-04-16, 最終更新日: 2025-10-29)

主引用文献

Cao, J.,Belousoff, M.J.,Johnson, R.M.,Keov, P.,Mariam, Z.,Deganutti, G.,Christopoulos, G.,Hick, C.A.,Reedtz-Runge, S.,Glendorf, T.,Ballarin-Gonzalez, B.,Raun, K.,Bayly-Jones, C.,Wootten, D.,Sexton, P.M.
Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors.
Nat Commun, 16:3389-3389, 2025

PubMed Abstract: 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.

PubMed: 40204768
DOI: 10.1038/s41467-025-58680-y

実験手法

ELECTRON MICROSCOPY (3.3 Å)