title: Functional analysis of a mutated analogue of the crustacean hyperglycaemic hormone from the crayfish Pontastacus leptodactylus.
abstract: The crustacean hyperglycaemic hormone (CHH), a pleiotropic neuropeptide, belongs to a family of structurally related peptides, having six cysteine residues in conserved positions forming three disulphide bridges, and regulating several physiological processes in crustaceans and insects. Structure-activity studies have shown that amidation of the C-terminus is important to confer biological activity to CHH. In this study we investigated the function of the d-Phe(3) of the N-terminal motif of Pontastacus leptodactylus CHH by a mutational analysis. The d-Phe in position 3 was substituted by a d-Ala and the functionality of the mutated analogue (Glp-d-A-CHH) was tested by in vivo biological assays. The mutated analogue resulted far less active than its wild-type counterparts, either in d- (Glp-d-CHH) or l- (Glp-l-CHH) configuration. These results suggest that Phe(3) is essential for the biological activity of P. leptodactylus CHH, demonstrating that also the N-terminus is involved in the binding with the receptor, and identifying in the Phe(3) a hot spot for the peptide-receptor binding.
authors: Department of Life Sciences, University of Trieste, Trieste, Italy.
authors: Alessandro
authors: A
authors: Mosco
authors: Ventsislav
authors: V
authors: Zlatev
authors: Corrado
authors: C
authors: Guarnaccia
authors: Piero G
authors: PG
authors: Giulianini
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D060829:Arthropod Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D003400:Astacoidea / Q000235:genetics; D004252:DNA Mutational Analysis; D007447:Invertebrate Hormones / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology
chemical_list: D060829:Arthropod Proteins; D007447:Invertebrate Hormones; D009419:Nerve Tissue Proteins; C015947:hyperglycemic hormone, crustacean