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RESEARCH ARTICLE
Contents Vol 73(3)

Phote-HrTH (Phormia terraenovae Hypertrehalosaemic Hormone), the Metabolic Hormone of the Fruit Fly: Solution Structure and Receptor Binding Model

Ibrahim A. Abdulganiyyu A , Marc-Antoine Sani https://orcid.org/0000-0003-3284-2176 C , Frances Separovic C , Heather Marco B and Graham E. Jackson A D
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa.

B Biological Sciences, University of Cape Town, Private Bag, Rondebosch, Cape Town 7701, South Africa.

C School of Chemistry, Bio21 Institute, University of Melbourne, Melbourne, Vic. 3010, Australia.

D Corresponding author. Email: graham.jackson@uct.ac.za

Australian Journal of Chemistry 73(3) 202-211 https://doi.org/10.1071/CH19461
Submitted: 18 September 2019  Accepted: 11 November 2019   Published: 17 January 2020

Abstract

Fruit flies are a widely distributed pest insect that pose a significant threat to food security. Flight is essential for the dispersal of the adult flies to find new food sources and ideal breeding spots. The supply of metabolic fuel to power the flight muscles of insects is regulated by adipokinetic hormones (AKHs). The fruit fly, Drosophila melanogaster, has the same AKH that is present in the blowfly, Phormia terraenovae; this AKH has the code-name Phote-HrTH. Binding of the AKH to the extra-cellular binding site of a G protein-coupled receptor causes its activation. In this paper, the structure of Phote-HrTH in sodium dodecyl sulfate (SDS) micelle solution was determined using NMR restrained molecular dynamics. The peptide was found to bind to the micelle and be fairly rigid, with an S2 order parameter of 0.96. The translated protein sequence of the AKH receptor from the fruit fly, D. melanogaster, Drome-AKHR, was used to construct two models of the receptor. It is proposed that these two models represent the active and inactive state of the receptor. The model based on the crystal structure of the β-2 adrenergic receptor was found to bind Phote-HrTH with a binding constant of −102 kJ mol−1, while the other model, based on the crystal structure of rhodopsin, did not bind the peptide. Under molecular dynamic simulation, in a palmitoyloleoylphosphatidylcholine (POPC) membrane, the receptor complex changed from an inactive to an active state. The identification and characterisation of the ligand binding site of Drome-AKHR provide novel information of ligand–receptor interaction, which could lead to the development of species-specific control substances to use discriminately against the fruit fly.


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