Mechanism of activation of the relaxin family peptide receptors RXFP1 and RXFP2

Abstract

The relaxin family peptide receptors RXFP1 and RXFP2 are the cognate receptors for the peptide hormones relaxin and INSL3 respectively, best known for their roles in reproductive biology. Being GPCRs, these receptors are members of the largest family of membrane-bound receptors known in the human genome, but they are unique within this family due to the existence of a single low-density lipoprotein type A (LDLa) module on the N-terminus of their large ectodomain. The LDLa module is imperative to normal receptor signalling and is hypothesised to be a tethered ligand, interacting with the receptor transmembrane domain (TMD) to bring about an active conformation. This module is connected to the..