9K3F
Cryo-EM structure of the unliganded human melanocortin receptor 3 (MC3R)-Gs complex
Summary for 9K3F
| Entry DOI | 10.2210/pdb9k3f/pdb |
| EMDB information | 62014 |
| Descriptor | Melanocortin receptor 3,Melanocortin receptor 3,Melanocortin receptor 3,LgBiT subunit, Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,HiBiT, ... (5 entities in total) |
| Functional Keywords | human melanocortin receptor 3, g protein-coupled receptor, unliganded, constitutive activity, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 174997.47 |
| Authors | Feng, W.B.,Zhou, Q.T.,Zheng, C.,Yang, D.H.,Wang, M.W. (deposition date: 2024-10-18, release date: 2025-08-06) |
| Primary citation | Feng, W.,Zhou, Q.,Zheng, C.,Yang, D.,Wang, M.W. Structural basis for the constitutive activity of the melanocortin receptor family. Structure, 33:1074-1087.e5, 2025 Cited by PubMed Abstract: The constitutive activity of melanocortin receptors (MCRs) is integral to several physiological processes. The unliganded cryo-electron microscopy structures of MC1R, MC2R, MC3R, MC4R, and MC5R in complex with G proteins determined at global resolutions of 2.98 Å, 3.01 Å, 2.75 Å, 3.12 Å, and 2.86 Å, respectively, revealed that their binding poses and interactions with G are similar to those of agonist-bound MCRs. The extracellular regions of the transmembrane helices (TMs) exhibit distinct conformational rearrangements, characterized by varying shifts of TM3 and outward displacements of TM4. These variations represent unique structural features of constitutively activated MCRs. Unassigned electron densities were observed within the orthosteric pockets where extensive interactions with cognate ligands occur. In addition, zinc ions, but not calcium, positively regulated MC4R activity in a dose-dependent manner. Our findings provide valuable insights into the molecular mechanisms underlying MCR basal activity and highlight the role of divalent ions in receptor activation. PubMed: 40157361DOI: 10.1016/j.str.2025.03.004 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.75 Å) |
Structure validation
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