9BLB
Human Calcitonin Receptor in Complex with Gs and Cagrilintide Backbone (non-acylated) in bypass conformation
Summary for 9BLB
| Entry DOI | 10.2210/pdb9blb/pdb |
| Related | 9BLC |
| EMDB information | 44652 |
| Descriptor | Cagrilintide backbone (non-acylated), Calcitonin receptor, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total) |
| Functional Keywords | amylin receptor, gpcr, ramps, calcitonin receptor, cagrilintide, obesity, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 6 |
| Total formula weight | 164992.13 |
| Authors | Cao, J.,Belousoff, M.J.,Wootten, D.L.,Sexton, P.M. (deposition date: 2024-04-30, release date: 2025-04-16, Last modification date: 2025-10-29) |
| Primary citation | 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 Cited by 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: 40204768DOI: 10.1038/s41467-025-58680-y PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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