Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town, 7701, South Africa.
Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town, 7701, South Africa; Current address, Department of Physics, Florida International University, Miami, 33199, FL, United States.
Int J Biol Macromol. 2018 Jan;106:969-978. doi: 10.1016/j.ijbiomac.2017.08.103. Epub 2017 Aug 22.
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 and Cys and an ionic lock between Arg and Thr and Thr. 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 β-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 -69kcalmol 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.
淡水溞（Daphnia pulex）红色素浓缩激素（RPCH）受体的一级序列被用于同源建模，构建了第一个甲壳类 G 蛋白偶联受体（Dappu-RPCHR）的三维模型。该受体属于 GPCR 家族 A 亚家族，具有 Cys 和 Cys 之间的二硫键以及 Arg 和 Thr 和 Thr 之间的离子锁。使用 NMR 约束分子动力学确定了在模拟膜环境中的激动剂 Dappu-RPCH 的结构。激动剂被发现具有一定的柔韧性，但在溶液中有两种主要构象，都具有β-转角。通过对接主要结构，在受体上找到了一个结合口袋。口袋的空间位置与冈比亚按蚊（Anopheles gambiae）的 AKH 受体相似。结合亲和力为-69kcalmol，Dappu-RPCH 的 N 端插入到 4 到 6 螺旋之间，C 端与细胞外环 ECL2 相互作用。结合后，与肽的氢键可能会激活受体。该 Dappu-RPCH/Dappu-RPCHR 模型的首次开发可能有助于理解甲壳类动物中的配体-受体相互作用。
