Elucidation of relaxin-3 binding interactions in the extracellular loops of RXFP3

摘要: Relaxin-3 is a highly conserved neuropeptide in vertebrate species and binds to the Class A G protein-coupled receptor (GPCR) RXFP3. involved wide range of behaviors, including feeding, stress responses, arousal, cognitive processes therefore targeting RXFP3 may be relevant for neurological diseases. Structural knowledge its interaction with relaxin-3 would both increase our understanding ligand recognition GPCRs that respond protein ligands enable acceleration design drug leads. In this study we have used comparative sequence analysis, molecular modeling mutagenesis investigate binding site native human (H3 relaxin) on receptor. Previous structure function studies demonstrated arginine residues H3 relaxin B-chain are critical interactions extracellular loops and/or N-terminal domain. Hence concentrated determining interacting sites these domains focused glutamic (E) aspartic acid (D) regions form electrostatic residues. Conserved D/E identified from multiple alignments were mutated Ala test effect loss amino side chain using Eu-labeled agonist. Finally data experiments been docking simulations homology model based peptide-bound chemokine 4 (CXCR4) structure. These resulted which will inform further interrogation agonist site.