8WOG
Cryo-EM structure of SUCR1 in complex with succinate and Gi protein
Summary for 8WOG
| Entry DOI | 10.2210/pdb8wog/pdb |
| EMDB information | 37686 |
| Descriptor | Succinate receptor 1, Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total) |
| Functional Keywords | gpcr, succinate receptor 1, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 119783.12 |
| Authors | |
| Primary citation | Liu, A.,Liu, Y.,Zhang, W.,Ye, R.D. Structural insights into ligand recognition and activation of the succinate receptor SUCNR1. Cell Rep, 43:114381-114381, 2024 Cited by PubMed Abstract: Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as a stress signal through succinate receptor (SUCNR1), a class A G protein-coupled receptor. Research on succinate signaling is hampered by the lack of high-resolution structures of the agonist-bound receptor. We present cryoelectron microscopy (cryo-EM) structures of SUCNR1-Gi complexes bound to succinate and its non-metabolite derivative cis-epoxysuccinate. Key determinants for the recognition of succinate in cis conformation include R281 and Y83, while Y30 and R99 participate in the binding of both succinate and cis-epoxysuccinate. Extracellular loop 2, through F175 in its β-hairpin, forms a hydrogen bond with succinate and caps the binding pocket. At the receptor-Gi interface, agonist binding induces the rearrangement of a hydrophobic network on transmembrane (TM)5 and TM6, leading to TM signaling through TM3 and TM7. These findings extend our understanding of succinate recognition by SUCNR1, aiding the development of therapeutics for the succinate receptor. PubMed: 38923454DOI: 10.1016/j.celrep.2024.114381 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.97 Å) |
Structure validation
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