Journal
GENERAL AND COMPARATIVE ENDOCRINOLOGY
Volume 177, Issue 3, Pages 332-337Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygcen.2012.04.025
Keywords
Adipokinetic hormone; Structure-activity relationship; Drosophila melanogaster; Anopheles gambiae; Adipokinetic hormone receptor; Cellular expression system
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Funding
- FWO [G0601.11]
- Concerted Research Action Programme (KU Leuven)
- National Research Foundation, Pretoria, South Africa [FA 2007021300002, IFR 2008071500048]
- Research Council of UCT
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Structure-activity studies for the adipokinetic hormone receptor of insects were for the first time performed in a cellular expression system. A series of single amino acid replacement analogues for the endogenous adipokinetic hormone of Drosophila melanogaster (pGlu-Leu-Thr-Phe-Ser-Pro-Asp-Trp-NH2) were screened for activity with a bioluminescence cellular assay, expressing the G-protein coupled receptor. For this series of peptide analogues, one amino acid of the N-terminal tetrapeptide was successively replaced by alanine, while those of the C-terminal tetrapeptide were successively substituted by glycine; other modifications included the blocked N- and C-termini that were replaced by an acetylated alanine and a hydroxyl group, respectively. The analogue series was tested on the AKH receptors of two dipteran species, D. melanogaster and Anopheles gambiae. The blocked termini of the AKH peptide probably play a minor role in receptor interaction and activation, but are considered functionally important elements to protect the peptide against exopeptidases. In contrast, the amino acids at positions 2, 3, 4 and 5 from the N-terminus all seem to be crucial for receptor activation. This can be explained by the potential presence of a beta-strand in this part of the peptide that interacts with the receptor. The inferred beta-strand is probably followed by a beta-turn in which the amino acids at positions 5-8 are involved. In this beta-turn, the residues at positions 6 and 8 seem to be essential, as their substitutions induce only a very low degree of receptor activation. Replacement of Asp(7), by contrast, does not influence receptor activation at all. This implies that its side chain is folded inside the beta-turn so that no interaction with the receptor occurs. (C) 2012 Elsevier Inc. All rights reserved.
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