Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH19461
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.


References

[1]  S. Sela, D. Nestel, R. Pinto, E. Nemny-Lavy, M. Bar-Joseph, Appl. Environ. Microbiol. 2005, 71, 4052.
         | Crossref | GoogleScholarGoogle Scholar | 16000820PubMed |

[2]  G. Gäde, H. G. Marco, in Handbook of Biologically Active Peptides (Ed. A. J. Kastin) 2013, pp. 185–190 (Academic Press: San Diego, CA).

[3]  G. Gäde, L. Auerswald, S. Afr. J. Zool. 1998, 33, 65.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  G. Gäde, L. Auerswald, Gen. Comp. Endocrinol. 2003, 132, 10.
         | Crossref | GoogleScholarGoogle Scholar | 12765639PubMed |

[5]  G. Gäde, H. G. Marco, J. Insect Physiol. 2009, 55, 1134.
         | Crossref | GoogleScholarGoogle Scholar | 19698718PubMed |

[6]  G. Gäde, Annu. Rev. Entomol. 2004, 49, 93.
         | Crossref | GoogleScholarGoogle Scholar | 14651458PubMed |

[7]  G. Gäde, Ann. N. Y. Acad. Sci. 2009, 1163, 125.
         | Crossref | GoogleScholarGoogle Scholar | 19456334PubMed |

[8]  G. Gäde, H. G. Marco, Stud. Nat. Prod. Chem. 2006, 33, 69.
         | Crossref | GoogleScholarGoogle Scholar |

[9]  H. G. Marco, G. Gäde, Physiol. Entomol. 2017, 42, 103.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  H. G. Marco, G. Gäde, Front. Endocrinol. 2019, 10, 231.
         | Crossref | GoogleScholarGoogle Scholar |

[11]  A. S. Hauser, M. M. Attwood, M. Rask-Andersen, H. B. Schiöth, D. E. Gloriam, Nat. Rev. Drug Discov. 2017, 16, 829.
         | Crossref | GoogleScholarGoogle Scholar | 29075003PubMed |

[12]  N. Audsley, R. E. Down, Insect Biochem. Mol. Biol. 2015, 67, 27.
         | Crossref | GoogleScholarGoogle Scholar | 26226649PubMed |

[13]  H. Verlinden, R. Vleugels, S. Zels, S. Dillen, C. Lenaerts, K. Crabbé, J. Spit, J. Vanden Broeck, Adv. Insect Physiol. 2014, 46, 167.
         | Crossref | GoogleScholarGoogle Scholar |

[14]  G. Gäde, H. Wilps, R. Kellner, Biochem. J. 1990, 269, 309.
         | Crossref | GoogleScholarGoogle Scholar | 2386478PubMed |

[15]  H. Wilps, G. Gäde, J. Insect Physiol. 1990, 36, 441.
         | Crossref | GoogleScholarGoogle Scholar |

[16]  M. H. Schaffer, B. E. Noyes, C. A. Slaughter, G. C. Thorne, S. J. Gaskell, Biochem. J. 1990, 269, 315.
         | Crossref | GoogleScholarGoogle Scholar | 2117437PubMed |

[17]  Q.-L. Hou, E.-H. Chen, H.-B. Jiang, D.-D. Wei, S.-H. Gui, J.-J. Wang, G. Smagghe, Insect Biochem. Mol. Biol. 2017, 90, 1.
         | Crossref | GoogleScholarGoogle Scholar | 28919559PubMed |

[18]  J. G. Stoffolano, K. Croke, J. Chambers, G. Gäde, P. Solari, A. Liscia, J. Insect Physiol. 2014, 71, 147.
         | Crossref | GoogleScholarGoogle Scholar | 25450427PubMed |

[19]  M. Bil, V. Broeckx, B. Landuyt, R. Huybrechts, Gen. Comp. Endocrinol. 2014, 208, 49.
         | Crossref | GoogleScholarGoogle Scholar | 25234055PubMed |

[20]  G. M. Attardo, A. M. M. Abd-Alla, A. Acosta-Serrano, J. E. Allen, R. Bateta, J. B. Benoit, K. Bourtzis, J. Caers, G. Caljon, M. B. Christensen, D. W. Farrow, M. Friedrich, A. Hua-Van, E. C. Jennings, D. M. Larkin, D. Lawson, M. J. Lehane, V. P. Lenis, E. Lowy-Gallego, R. W. Macharia, A. R. Malacrida, H. G. Marco, D. Masiga, G. L. Maslen, I. Matetovici, R. P. Meisel, I. Meki, V. Michalkova, W. J. Miller, P. Minx, P. O. Mireji, L. Ometto, A. G. Parker, R. Rio, C. Rose, A. J. Rosendale, O. Rota-Stabelli, G. Savini, L. Schoofs, F. Scolari, M. T. Swain, P. Takáč, C. Tomlinson, G. Tsiamis, J. Van Den Abbeele, A. Vigneron, J. Wang, W. C. Warren, R. M. Waterhouse, M. T. Weirauch, B. L. Weiss, R. K. Wilson, X. Zhao, S. Aksoy, Genome Biol. 2019, 20, 187.
         | Crossref | GoogleScholarGoogle Scholar | 31477173PubMed |

[21]  Y. Park, Y. J. Kim, M. E. Adams, Proc. Natl. Acad. Sci. USA 2002, 99, 11423.
         | Crossref | GoogleScholarGoogle Scholar | 12177421PubMed |

[22]  F. Staubli, T. J. D. Jørgensen, G. Cazzamali, M. Williamson, C. Lenz, L. Søndergaard, P. Roepstorff, C. J. P. Grimmelikhuijzen, Proc. Natl. Acad. Sci. USA 2002, 99, 3446.
         | Crossref | GoogleScholarGoogle Scholar | 11904407PubMed |

[23]  I. Marcotte, F. Separovic, M. Gagné, S. M. Auger, Biophys. J. 2004, 86, 1587.
         | Crossref | GoogleScholarGoogle Scholar | 14990485PubMed |

[24]  M.-A. Sani, F. Separovic, Acc. Chem. Res. 2016, 49, 1130.
         | Crossref | GoogleScholarGoogle Scholar | 27187572PubMed |

[25]  L. Eidenschink, B. L. Kier, K. N. L. Huggins, N. H. Andersen, Proteins 2009, 75, 308.
         | Crossref | GoogleScholarGoogle Scholar | 18831035PubMed |

[26]  L. Szilágyi, Prog. Nucl. Magn. Reson. Spectrosc. 1995, 27, 325.
         | Crossref | GoogleScholarGoogle Scholar |

[27]  G. E. Jackson, R. Gamieldien, G. Mugumbate, G. Gäde, Peptides 2014, 53, 270.
         | Crossref | GoogleScholarGoogle Scholar | 24444447PubMed |

[28]  G. E. Jackson, E. Pavadai, G. Gäde, Z. Timol, N. H. Andersen, Int. J. Biol. Macromol. 2018, 106, 969.
         | Crossref | GoogleScholarGoogle Scholar | 28837848PubMed |

[29]  M. L. Tremblay, A. W. Banks, J. K. Rainey, J. Biomol. NMR 2010, 46, 257.
         | Crossref | GoogleScholarGoogle Scholar | 20213252PubMed |

[30]  M. S. Cheung, M. L. Maguire, T. J. Stevens, R. W. Broadhurst, J. Magn. Reson. 2010, 202, 223.
         | Crossref | GoogleScholarGoogle Scholar | 20015671PubMed |

[31]  W. Rieping, M. Habeck, B. Bardiaux, A. Bernard, T. E. Malliavin, M. Nilges, Bioinformatics 2007, 23, 381.
         | Crossref | GoogleScholarGoogle Scholar | 17121777PubMed |

[32]  V. B. Chen, W. B. Arendall, J. J. Headd, D. A. Keedy, R. M. Immormino, G. J. Kapral, L. W. Murray, J. S. Richardson, D. C. Richardson, Acta Crystallogr. D Biol. Crystallogr. 2010, 66, 12.
         | Crossref | GoogleScholarGoogle Scholar | 20057044PubMed |

[33]  P. F. J. Fuchs, A. J. P. Alix, Proteins 2005, 59, 828.
         | Crossref | GoogleScholarGoogle Scholar |

[34]  G. E. Jackson, E. Pavadai, G. Gäde, N. H. Andersen, PeerJ 2019, 7, e7514.
         | Crossref | GoogleScholarGoogle Scholar | 31531269PubMed |

[35]  C. Giragossian, M. Pellegrini, D. F. Mierke, Can. J. Physiol. Pharmacol. 2002, 80, 383.
         | Crossref | GoogleScholarGoogle Scholar | 12056543PubMed |

[36]  L. J. McGuffin, K. Bryson, D. T. Jones, Bioinformatics 2000, 16, 404.
         | Crossref | GoogleScholarGoogle Scholar | 10869041PubMed |

[37]  H. M. Berman, Acta Crystallogr. A 2008, 64, 88.
         | Crossref | GoogleScholarGoogle Scholar | 18156675PubMed |

[38]  H. M. Berman, G. J. Kleywegt, H. Nakamura, J. L. Markley, J. Comput. Aided Mol. Des. 2014, 28, 1009.
         | Crossref | GoogleScholarGoogle Scholar | 25062767PubMed |

[39]  P. Chelikani, V. Hornak, M. Eilers, P. J. Reeves, S. O. Smith, U. L. RajBhandary, H. G. Khorana, Proc. Natl. Acad. Sci. USA 2007, 104, 7027.
         | Crossref | GoogleScholarGoogle Scholar | 17438264PubMed |

[40]  N. Guex, M. C. Peitsch, T. Schwede, Electrophoresis 2009, 30, S162.
         | Crossref | GoogleScholarGoogle Scholar | 19517507PubMed |

[41]  Z. T. Farahbakhsh, K. D. Ridge, H. G. Khorana, W. L. Hubbell, Biochemistry 1995, 34, 8812.
         | Crossref | GoogleScholarGoogle Scholar | 7612622PubMed |

[42]  C. Y. Huang, V. Olieric, P. Ma, N. Howe, L. Vogeley, X. Liu, R. Warshamanage, T. Weinert, E. Panepucci, B. Kobilka, K. Diederichs, M. Wang, M. Caffrey, Acta Crystallogr. D Struct. Biol. 2016, 72, 93.
         | Crossref | GoogleScholarGoogle Scholar | 26894538PubMed |

[43]  J. Standfuss, P. C. Edwards, A. Dantona, M. Fransen, G. Xie, D. D. Oprian, G. F. X. Schertler, Nature 2011, 471, 656.
         | Crossref | GoogleScholarGoogle Scholar | 21389983PubMed |

[44]  C. E. Elling, T. W. Schwartz, EMBO J. 1996, 15, 6213.
         | Crossref | GoogleScholarGoogle Scholar | 8947044PubMed |

[45]  V. Cherezov, D. M. Rosenbaum, M. A. Hanson, S. G. F. Rasmussen, F. S. Thian, T. S. Kobilka, H.-J. Choi, P. Kuhn, W. I. Weis, B. K. Kobilka, R. C. Stevens, Science 2007, 318, 1258.
         | Crossref | GoogleScholarGoogle Scholar | 17962520PubMed |

[46]  U. Gether, Endocr. Rev. 2000, 21, 90.
         | Crossref | GoogleScholarGoogle Scholar | 10696571PubMed |

[47]  R. O. Dror, D. H. Arlow, D. W. Borhani, M. Ø. Jensen, S. Piana, D. E. Shaw, Proc. Natl. Acad. Sci. USA 2009, 106, 4689.
         | Crossref | GoogleScholarGoogle Scholar | 19258456PubMed |

[48]  T. Chum, D. Glatzová, Z. Kvíčalová, Z. Kvíčalová, J. Malínský, T. Brdička, M. Cebecauer, J. Cell Sci. 2016, 129, 95.
         | Crossref | GoogleScholarGoogle Scholar | 26585312PubMed |

[49]  G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S. Goodsell, A. J. Olson, J. Comput. Chem. 2009, 30, 2785.
         | Crossref | GoogleScholarGoogle Scholar | 19399780PubMed |

[50]  C. R. Corbeil, C. I. Williams, P. Labute, J. Comput. Aided Mol. Des. 2012, 26, 775.
         | Crossref | GoogleScholarGoogle Scholar | 22566074PubMed |

[51]  T. J. Halgren, J Chem Inf Model 2009, 49, 377.
         | Crossref | GoogleScholarGoogle Scholar |

[52]  G. Mugumbate, G. E. Jackson, D. van der Spoel, K. E. Kövér, L. Szilágyi, Peptides 2013, 41, 94.
         | Crossref | GoogleScholarGoogle Scholar | 23439319PubMed |

[53]  K. Palczewski, T. Kumasaka, T. Hori, C. A. Behnke, H. Motoshima, B. A. Fox, I. Le Trong, D. C. Teller, T. Okada, R. E. Stenkamp, M. Yamamoto, M. Miyano, Science 2000, 289, 739.
         | Crossref | GoogleScholarGoogle Scholar | 10926528PubMed |

[54]  J. P. Vilardaga, M. Bünemann, C. Krasell, M. Castro, M. J. Lohse, Nat. Biotechnol. 2003, 21, 807.
         | Crossref | GoogleScholarGoogle Scholar | 12808462PubMed |

[55]  M. Rasmussen, M. Leander, S. Ons, R. Nichols, Peptides 2015, 71, 259.
         | Crossref | GoogleScholarGoogle Scholar | 26211890PubMed |

[56]  G. Swaminath, X. Deupi, T. W. Lee, W. Zhu, F. S. Thian, T. S. Kobilka, B. Kobilka, J. Biol. Chem. 2005, 280, 22165.
         | Crossref | GoogleScholarGoogle Scholar | 15817484PubMed |

[57]  W. F. Vranken, W. Boucher, T. J. Stevens, R. H. Fogh, A. Pajon, M. Llinas, E. L. Ulrich, J. L. Markley, J. Ionides, E. D. Laue, Proteins 2005, 59, 687.
         | Crossref | GoogleScholarGoogle Scholar | 15815974PubMed |

[58]  D. Van der Spoel, E. Lindahl, B. Hess, G. Groenhof, A. E. Mark, H. J. C. Berendsen, J. Comput. Chem. 2005, 26, 1701.
         | Crossref | GoogleScholarGoogle Scholar | 16211538PubMed |

[59]  G. E. Jackson, A. N. Mabula, S. R. Stone, G. Gäde, K. E. Kövér, L. Szilágyi, D. van der Spoel, Peptides 2009, 30, 557.
         | Crossref | GoogleScholarGoogle Scholar | 19103242PubMed |

[60]  D. P. Tieleman, D. van der Spoel, H. J. C. Berendsen, J. Phys. Chem. B 2000, 104, 6380.
         | Crossref | GoogleScholarGoogle Scholar |

[61]  R. A. Laskowski, J. A. C. Rullmann, M. W. MacArthur, J. M. R. Kaptein, J. Biomol. NMR 1996, 8, 477.
         | Crossref | GoogleScholarGoogle Scholar | 9008363PubMed |

[62]  S. Vilar, G. Ferino, S. S. Phatak, B. Berk, C. N. Cavasotto, S. Costanzi, J. Mol. Graph. Model. 2011, 29, 614.
         | Crossref | GoogleScholarGoogle Scholar | 21146435PubMed |

[63]  Y. Lee, S. Basith, S. Choi, J. Med. Chem. 2018, 61, 1.
         | Crossref | GoogleScholarGoogle Scholar | 28657745PubMed |

[64]  Y. Li, T. Hou, W. Goddard, Curr. Med. Chem. 2010, 17, 1167.
         | Crossref | GoogleScholarGoogle Scholar | 20158474PubMed |

[65]  A. J. Kooistra, S. Kuhne, I. J. P. de Esch, R. Leurs, C. de Graaf, Br. J. Pharmacol. 2013, 170, 101.
         | Crossref | GoogleScholarGoogle Scholar | 23713847PubMed |

[66]  S. Jo, J. B. Lim, J. B. Klauda, Biophys. J. 2009, 97, 50.
         | Crossref | GoogleScholarGoogle Scholar | 19580743PubMed |