Conserved molecular switch interactions in modeled cardioactive RF-NH2 peptide receptors: Ligand binding and activation.

Peptides may act through G protein-coupled receptors to influence cardiovascular performance; thus, delineating mechanisms involved in signaling is a molecular-based strategy to influence health. Molecular switches, often represented by conserved motifs, maintain a receptor in an inactive state. However, once the switch is broken, the transmembrane regions move and activation occurs. The molecular switches of Drosophila melanogaster myosuppressin (MS) receptors were previously identified to include a unique ionic lock and novel 3-6 lock, as well as transmission and tyrosine toggle switches. In addition to MS, cardioactive ligands structurally related by a C-terminal RF-NH 2 include sulfakinin, neuropeptide F (NPF), short NPF, and FMRF-NH 2 -containing peptide subfamilies. We hypothesized receptor molecular switch motifs were conserved within a RF-NH 2 subfamily and across species. Thus, we investigated RF-NH 2 receptor (RFa-R) molecular switches in D. melanogaster , Tribolium castaneum , Anopheles gambiae , Rhodnius prolixus , and Bombyx mori . Adipokinetic hormone (AKH), which does not contain a RF-NH 2 , was also examined. The tyrosine toggle switch and ionic lock showed a higher degree of conservation within a RF-NH 2 subfamily than the transmission switch and 3-7 lock. AKH receptor motifs were not representative of a RF-NH 2 subfamily. The motifs and interactions of switches in the RFa-Rs were consistent with receptor activation and ligand-specific binding. [ABSTRACT FROM AUTHOR]