Interaction of the red pigment-concentrating hormone of the crustacean Daphnia pulex, with its cognate receptor, Dappu-RPCHR: A nuclear magnetic resonance and modeling study

The primary sequence of the red pigment-concentrating hormone (RPCH) receptor of the water flea, Daphnia pulex, was used in homology modeling to construct the first 3D model of a crustacean G-protein coupled receptor, Dappu-RPCHR. This receptor was found to belong to the class A subfamily of GPCRs with a disulfide bridge between Cys(72) and Cys(150) and an ionic lock between Arg(97) and Thr(224) and Thr(220). NMR restrained molecular dynamics was used to determine the structure of an agonist, Dappu-RPCH, in a membrane-mimicking environment. The agonist was found to be flexible but has two main conformations in solution, both having beta-turns. Docking of the predominant structure was used to find a binding pocket on the receptor. The pocket's spatial location was similar to that of the AKH receptor of Anopheles gambiae. The binding affinity was 69 kcal mol(-1) with the N-terminus of Dappu-RPCH inserted between helices 4 and 6, and the C-terminus interacting with extra-cellular loop, ECL2. Upon binding, H-bonding to the peptide may activate the receptor. This development of the first Dappu-RPCH/Dappu-RPCHR model could be useful for understanding ligand-receptor interactions in crustaceans. (C) 2017 Elsevier By. All rights reserved.