25IK
Cryo-EM structure of MasR(FL)-Gq
Summary for 25IK
| Entry DOI | 10.2210/pdb25ik/pdb |
| EMDB information | 80137 |
| Descriptor | Soluble cytochrome b562,Proto-oncogene Mas,LgBiT tag, Gs-mini-Gq chimera, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (5 entities in total) |
| Functional Keywords | gpcr, signaling protein, membrane protein |
| Biological source | Escherichia coli More |
| Total number of polymer chains | 5 |
| Total formula weight | 174538.09 |
| Authors | |
| Primary citation | Suzuki, S.,Tanaka, K.,Nishikawa, K.,Fujiyoshi, Y. Cryo-EM structure of the human Mas receptor reveals N-terminal occlusion of the orthosteric ligand binding pocket. J.Mol.Biol., :169844-169844, 2026 Cited by PubMed Abstract: The Mas receptor (MasR) is a class A G protein-coupled receptor (GPCR) that mediates the counter-regulatory arm of the renin-angiotensin system through the ACE2-angiotensin-(1-7)-MasR axis and represents a promising therapeutic target for cardiovascular and metabolic disease. Despite its physiological importance, the structural basis of MasR has remained unknown. Here we report cryo-EM structures of human MasR in complex with heterotrimeric Gq at resolutions of 2.9 Å and 3.1 Å, determined for the full-length receptor and an N-terminally truncated variant (del2-25), respectively. These structures reveal that the receptor's own N-terminal peptide (residues 2-11) threads into and occludes the orthosteric binding pocket, functioning as an endogenous pseudo ligand. Functional mutagenesis and molecular dynamics simulations demonstrate that this N-terminal cap stably occupies the pocket but is dispensable for constitutive Gq coupling, distinguishing MasR from other N-terminal cap-forming GPCRs. Structural comparison with Mrgpr family members reveals a conserved Gq-coupling interface at the cytoplasmic face alongside divergent extracellular pocket architectures and identifies Y252 as a structural element that occludes a conserved sub-pocket present in Mrgpr paralogs. Molecular docking simulation of the MasR agonist AR234960 provides a structural template for orthosteric ligand design. Together, these findings establish the structural framework for MasR. PubMed: 42105974DOI: 10.1016/j.jmb.2026.169844 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
Download full validation report
