We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Resolving the Unconventional Mechanisms Underlying RXFP1 and RXFP2 Receptor Function.
- Authors
Hartley, Brigham J.; Scott, Daniel J.; Callander, Gabrielle E.; Wilkinson, Tracey N.; Ganella, Despina E.; Kong, Chze K.; Layfield, Sharon; Ferraro, Tania; Petrie, Emma J.; Bathgate, Ross A. D.
- Abstract
The receptors for relaxin and insulin-like peptide 3 (INSL3) are now well-characterized as the relaxin family peptide (RXFP) receptors RXFP1 and RXFP2, respectively. They are G-protein-coupled receptors (GPCRs) with closest similarity to the glycoprotein hormone receptors, with both containing large ectodomains with 10 leucine-rich repeats (LRRs). Additionally, RXFP1 and RXFP2 are unique in the LGR family in that they contain a low-density lipoprotein class A (LDL-A) module at their N-terminus. Ligand-mediated activation of RXFP1 and RXFP2 is a complex process involving various domains of the receptors. Primary ligand binding occurs via interactions between B-chain residues of the peptides with specific residues in the LRRs of the ectodomain. There is a secondary binding site in the transmembrane exoloops which may interact with the A chain of the peptides. Receptor signaling through cAMP then requires the unique LDL-A module, as receptors without this domain bind ligand normally but do not signal. This is an unconventional mode of activation for a GPCR, and the precise mode of action of the LDL-A module is currently unknown. The specific understanding of the mechanisms underlying ligand-mediated activation of RXFP1 and RXFP2 is crucial in terms of targeting these receptors for future drug development.
- Subjects
CELL receptors; RELAXIN; PEPTIDES; GLYCOPROTEINS; LIPOPROTEIN A; LIGAND binding (Biochemistry)
- Publication
Annals of the New York Academy of Sciences, 2009, Vol 1160, p67
- ISSN
0077-8923
- Publication type
Article
- DOI
10.1111/j.1749-6632.2009.03949.x