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-Structure paper
Title | The relaxin receptor RXFP1 signals through a mechanism of autoinhibition. |
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Journal, issue, pages | Nat Chem Biol, Vol. 19, Issue 8, Page 1013-1021, Year 2023 |
Publish date | Apr 20, 2023 |
Authors | Sarah C Erlandson / Shaun Rawson / James Osei-Owusu / Kelly P Brock / Xinyue Liu / Joao A Paulo / Julian Mintseris / Steven P Gygi / Debora S Marks / Xiaojing Cong / Andrew C Kruse / |
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 ...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. |
External links | Nat Chem Biol / PubMed:37081311 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.2 - 4.2 Å |
Structure data | EMDB-26003, PDB-7tmw: EMDB-26004: Cryo-EM map of the full-length relaxin receptor RXFP1 in complex with heterotrimeric Gs |
Source |
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Keywords | MEMBRANE PROTEIN / GPCR / Complex / Signaling |