7TMW
Cryo-EM structure of the relaxin receptor RXFP1 in complex with heterotrimeric Gs
Summary for 7TMW
| Entry DOI | 10.2210/pdb7tmw/pdb |
| EMDB information | 26003 |
| Descriptor | Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (4 entities in total) |
| Functional Keywords | gpcr, complex, signaling, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 177282.42 |
| Authors | Erlandson, S.C.,Rawson, S.,Kruse, A.C. (deposition date: 2022-01-20, release date: 2023-02-15, Last modification date: 2024-11-13) |
| Primary citation | Erlandson, S.C.,Rawson, S.,Osei-Owusu, J.,Brock, K.P.,Liu, X.,Paulo, J.A.,Mintseris, J.,Gygi, S.P.,Marks, D.S.,Cong, X.,Kruse, A.C. The relaxin receptor RXFP1 signals through a mechanism of autoinhibition. Nat.Chem.Biol., 19:1013-1021, 2023 Cited by PubMed Abstract: The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and leucine-rich repeats. The mechanism of RXFP1 signal transduction is clearly distinct from that of other GPCRs, but remains very poorly understood. In the present study, we determine the cryo-electron microscopy structure of active-state human RXFP1, bound to a single-chain version of the endogenous agonist relaxin-2 and the heterotrimeric G protein. Evolutionary coupling analysis and structure-guided functional experiments reveal that RXFP1 signals through a mechanism of autoinhibition. Our results explain how an unusual GPCR family functions, providing a path to rational drug development targeting the relaxin receptors. PubMed: 37081311DOI: 10.1038/s41589-023-01321-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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