Conserved residues in RF-NH sub(2) receptor models identify predicted contact sites in ligand-receptor binding

Peptides in the RF-NH sub(2) family are grouped together based on an amidated dipeptide C terminus and signal through G-protein coupled receptors (GPCRs) to influence diverse physiological functions. By determining the mechanisms underlying RF-NH sub(2) signaling targets can be identified to modulat...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2014-03, Vol.53, p.278-285
Main Authors: Bass, C, Katanski, C, Maynard, B, Zurro, I, Mariane, E, Matta, M, Loi, M, Melis, V, Capponi, V, Muroni, P, Setzu, M, Nichols, R
Format: Article
Language:English
Subjects:
Binding
Contact
Ligands
Mathematical models
Peptides
Pocket
Receptors
Residues
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Summary:Peptides in the RF-NH sub(2) family are grouped together based on an amidated dipeptide C terminus and signal through G-protein coupled receptors (GPCRs) to influence diverse physiological functions. By determining the mechanisms underlying RF-NH sub(2) signaling targets can be identified to modulate physiological activity; yet, how RF-NH sub(2) peptides interact with GPCRs is relatively unexplored. We predicted conserved residues played a role in Drosophila melanogaster RF-NH sub(2) ligand-receptor interactions. In this study D. melanogaster rhodopsin-like family A peptide GPCRs alignments identified eight conserved residues unique to RF-NH sub(2) receptors. Three of these residues were in extra-cellular loops of modeled RF-NH sub(2) receptors and four in transmembrane helices oriented into a ligand binding pocket to allow contact with a peptide. The eighth residue was unavailable for interaction; yet its conservation suggested it played another role. A novel hydrophobic region representative of RF-NH sub(2) receptors was also discovered. The presence of rhodopsin-like family A GPCR structural motifs including a toggle switch indicated RF-NH sub(2)s signal classically; however, some features of the DMS receptors were distinct from other RF-NH sub(2) GPCRs. Additionally, differences in RF-NH sub(2) receptor structures which bind the same peptide explained ligand specificity. Our novel results predicted conserved residues as RF-NH sub(2) ligand-receptor contact sites and identified unique and classic structural features. These discoveries will aid antagonist design to modulate RF-NH sub(2) signaling.
ISSN:0196-9781
DOI:10.1016/j.peptides.2013.06.009