6IBB
Crystal structure of the rat isoform of the succinate receptor SUCNR1 (GPR91) in complex with a nanobody
Summary for 6IBB
| Entry DOI | 10.2210/pdb6ibb/pdb |
| Descriptor | Succinate receptor 1, Nanobody6, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate, ... (7 entities in total) |
| Functional Keywords | sucnr1 gpr91 gpcr g-protein coupled receptor nanobody succinate complex, membrane protein |
| Biological source | Rattus norvegicus (Norway Rat) More |
| Total number of polymer chains | 4 |
| Total formula weight | 116776.95 |
| Authors | Haffke, M.,Jaakola, V.-P. (deposition date: 2018-11-29, release date: 2019-08-14, Last modification date: 2024-10-23) |
| Primary citation | Haffke, M.,Fehlmann, D.,Rummel, G.,Boivineau, J.,Duckely, M.,Gommermann, N.,Cotesta, S.,Sirockin, F.,Freuler, F.,Littlewood-Evans, A.,Kaupmann, K.,Jaakola, V.P. Structural basis of species-selective antagonist binding to the succinate receptor. Nature, 574:581-585, 2019 Cited by PubMed Abstract: The tricarboxylic acid cycle intermediate succinate is involved in metabolic processes and plays a crucial role in the homeostasis of mitochondrial reactive oxygen species. The receptor responsible for succinate signalling, SUCNR1 (also known as GPR91), is a member of the G-protein-coupled-receptor family and links succinate signalling to renin-induced hypertension, retinal angiogenesis and inflammation. Because SUCNR1 senses succinate as an immunological danger signal-which has relevance for diseases including ulcerative colitis, liver fibrosis, diabetes and rheumatoid arthritis-it is of interest as a therapeutic target. Here we report the high-resolution crystal structure of rat SUCNR1 in complex with an intracellular binding nanobody in the inactive conformation. Structure-based mutagenesis and radioligand-binding studies, in conjunction with molecular modelling, identified key residues for species-selective antagonist binding and enabled the determination of the high-resolution crystal structure of a humanized rat SUCNR1 in complex with a high-affinity, human-selective antagonist denoted NF-56-EJ40. We anticipate that these structural insights into the architecture of the succinate receptor and its antagonist selectivity will enable structure-based drug discovery and will further help to elucidate the function of SUCNR1 in vitro and in vivo. PubMed: 31645725DOI: 10.1038/s41586-019-1663-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.12 Å) |
Structure validation
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