9DQH
CryoEM structure of Gq-coupled MRGPRD with a new agonist EP-2825
This is a non-PDB format compatible entry.
Summary for 9DQH
| Entry DOI | 10.2210/pdb9dqh/pdb |
| EMDB information | 47113 |
| Descriptor | Mas-related G-protein coupled receptor member D, Gs-mini-Gq chimera, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total) |
| Functional Keywords | gpcr, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 137684.19 |
| Authors | Cao, C.,Wang, C.,Liu, Y.,Fay, J.F.,Roth, B.L. (deposition date: 2024-09-24, release date: 2024-12-11, Last modification date: 2025-05-28) |
| Primary citation | Wang, C.,Liu, Y.,Lanier, M.,Yeager, A.,Singh, I.,Gumpper, R.H.,Krumm, B.E.,DeLeon, C.,Zhang, S.,Boehm, M.,Pittner, R.,Baron, A.,Dvorak, L.,Bacon, C.,Shoichet, B.K.,Martinborough, E.,Fay, J.F.,Cao, C.,Roth, B.L. High-affinity agonists reveal recognition motifs for the MRGPRD GPCR. Cell Rep, 43:114942-114942, 2024 Cited by PubMed Abstract: The human MRGPRD protein is a member of the Mas-related G protein-coupled receptors (MRGPRs) that is involved in the sensing of pain, itch, and other inflammatory stimuli. As with other MRGPRs, MRGPRD is a relatively understudied receptor with few known agonists. The most potent small-molecule agonist of MRGPRD reported so far is β-alanine, with an affinity in the micromole range, which largely restricts its functional study. Here, we report two MRGPRD agonists, EP-2825 and EP-3945, that are approximately 100-fold more potent than β-alanine and determine the structures of MRGPRD-Gq in complex with EP-2825 and EP-3945, respectively. The structures reveal distinct agonist binding modes of MRGPRD and large conformational plasticity of the orthosteric pocket. Collectively, the discovery of high-affinity MRGPRD agonists and their distinct binding modes will facilitate the functional study and the structure-based design of ligands targeting this understudied receptor. PubMed: 39580805DOI: 10.1016/j.celrep.2024.114942 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.92 Å) |
Structure validation
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