Modeling the Primary Hormone-Binding Site of RXFP1 and RXFP2

• Published in: Annals of the New York Academy of Sciences Vol. 1160; no. 1; pp. 74 - 77
• Main Authors: Scott, Daniel J., Tregear, Geoffrey W., Bathgate, Ross A. D.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.04.2009
• Subjects: Binding Sites; GPCR; Humans; LDL-A; LGR7; LGR8; Models, Molecular; molecular modeling; Protein Binding; Protein Structure, Tertiary; Receptors, G-Protein-Coupled - chemistry; Receptors, G-Protein-Coupled - metabolism; Receptors, Peptide - chemistry; Receptors, Peptide - metabolism; Relaxin - chemistry; Relaxin - metabolism; RXFP1; RXFP2
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2009.03950.x

The primary binding sites of the relaxin and insulin‐like peptide 3 (INSL3) receptors, RXFP1 and RXFP2, are found within the leucine‐rich repeats (LRRs) of the ectodomains. Specific B‐chain residues in the peptides interact with residues in the inner β‐sheets of the LRRs of the receptors. Relaxin binds to RXFP2 with high affinity, although INSL3 has a very poor affinity for RXFP1. In this paper we present evidence that relaxin binds to the LRRs of RXFP2 in a manner similar to INSL3 binding to its receptor. Additionally, we introduce a model of this binding interaction and compare it to an alternate model for relaxin–RXFP1 binding.