| Title: | "Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori" |
| Author(s): | Shen Z; Jiang X; Yan L; Chen Y; Wang W; Shi Y; Shi L; Liu D; Zhou N; |
| Address: | "Department of Economic Zoology, College of Animal Sciences, Zhejiang University, Hangzhou, China. Institute of Biochemistry, College of Life Sciences, Zhejiang University, Hangzhou, China. Department of Pharmacology III, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China" |
| ISSN/ISBN: | 1530-6860 (Electronic) 0892-6638 (Linking) |
| Abstract: | "Diapause hormone (DH) is a 24-aa amidated neuropeptide that elicits the embryonic diapause of the silkworm, Bombyx mori ( Bommo), via sensitive and selective interaction with its receptor, Bommo DH receptor ( Bommo-DHR). Previous studies of the structure-activity relationship of Bommo-DH were all based on an in vivo diapause-induction bioassay, which has provided little information on the structure of Bommo-DHR or its iteration with DH. Here, to unveil the interaction of Bommo-DH with its receptor, N-terminally truncated analogs and alanine-scanning mutants of Bommo-DH were chemically synthesized and functionally evaluated by using a Cy5.5-labeled Bommo-DH competitive binding assay and Bommo-DHR-based functional assays, including cAMP assay and Ca(2+) mobilization assay. Our study demonstrates that the C-terminal residues of Arg23 and Leu24 of Bommo-DH are essential for the binding and activation of Bommo-DHR, and that Trp19 and Phe20 also contribute to the functional activity of Bommo-DH. In contrast, when Gly21 or Pro22 were replaced with alanine, both mutants exhibited binding and signaling activities that were indistinguishable from the wild-type peptide. Furthermore, our homology modeling and molecular dynamics simulations, together with experimental validations, have identified the residues of Glu89, Phe172, Phe194, and Tyr299 in Bommo-DHR that are critically involved in the interaction with Bommo-DH. These results may deepen our understanding of the interactions of class-A GPCRs with their peptidic ligands, particularly those between pheromone biosynthesis-activating neuropeptide/DH family neuropeptides and their cognate receptors.-Shen, Z., Jiang, X., Yan, L., Chen, Y., Wang, W., Shi, Y., Shi, L., Liu, D., Zhou, N. Structural basis for the interaction of diapause hormone with its receptor in the silkworm, Bombyx mori" |
| Keywords: | "Amino Acid Sequence Animals Bombyx Insect Proteins/*chemistry/*metabolism Neuropeptides/*chemistry/*metabolism Protein Conformation Receptors, Cell Surface/*chemistry/*metabolism Signal Transduction Gpcr neuropeptide signaling structure-activity relations;" |
| Notes: | "MedlineShen, Zhangfei Jiang, Xue Yan, Lili Chen, Yu Wang, Weiwei Shi, Ying Shi, Liangen Liu, Dongxiang Zhou, Naiming eng Research Support, Non-U.S. Gov't 2017/11/05 FASEB J. 2018 Mar; 32(3):1338-1353. doi: 10.1096/fj.201700931R. Epub 2018 Jan 3" |
