Ligand binding properties of human galanin receptors

Abstract

The galanin receptor family comprises of three members, GalR1, GalR2 and GalR3, all belonging to the G-protein-couple receptor superfamily. All three receptors bind the peptide hormone galanin, but show distinctly different binding properties to other molecules and effects on intracellular signaling. To gain insight on the molecular basis of receptor subtype specificity, we have generated a three-dimensional model for each of the galanin receptors based on its homologs in the same family. We found significant differences in the organization of the binding pockets among the three types of receptors, which might be the key for specific molecular recognition of ligands. Through docking of fragments of the galanin peptide and a number of ligands, we investigated the involvement of transmembrane and loop residues in ligand interaction.

Keywords::

• Galanin receptors
• GPCR modeling
• ligand binding

Acknowledgements

The EU 7th Framework Program is gratefully acknowledged for support to the EDICT project, contract No: FP7-HEALTH-F4-2007-201924. This work was also supported by grants from the Swedish National Research Councils and SSF (the Foundation for Strategic Research) to AE.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.