Utilizing the innovative HiBiT tag to mark relaxin receptors on cell surfaces for BRET proximity experiments

Abstract

Because its corresponding pep-tide ligand, relaxin, has therapeutic promise, the Relaxin family peptide 1 (RXFP1) receptor, a

Class A G protein‐coupled receptor (GPCR), is highly sought after as a potential pharmacological target. 1, 2 This Class A

GPCR, RXFP1, stands out due to its unusually large extracellular domain, which includes an N-terminal low-density

lipoprotein class A (LDLa) module before the so-called "linker" that connects the LDLa module to a domain that contains 10

leucine-rich repeats (LRR) (Figure 1A). 3 There are two locations where high-affinity relaxin binding may take place: one in

the LRR4,5 and one in the linker. 6 The LDLa module is crucial for receptor activation in both RXFP1 and RXFP2, the only

mammalian GPCRs that possess it (the receptor for insu‐ lin‐like peptide 3).