Isolation, identification and functional significance of [Hyp2]Met-callatostatin and des Gly-Pro Met-callatostatin, two further post-translational modifications of the blowfly neuropeptide Met-callatostatin.
Two post-translationally modified neuropeptides of the Met-callatostatin (Gly-Pro-Pro-Tyr-Asp-Phe-Gly-Met-NH2) family have been identified from head extracts of the blowfly Calliphora vomitoria. They are the octapeptide, [Hyp2]Met-callatostatin, (Gly-Hyp-Pro-Tyr-Asp-Phe-Gly-Met-NH2) and the truncated hexapeptide, des Gly-Pro Met-callatostatin (Pro-Tyr-Asp-Phe-Gly-Met-NH2). The existence of the [Hyp2]Met-callatostatin variant, in addition to the previously identified [Hyp3]Met-callatostatin peptide, suggests that the motif for prolyl hydroxylation in C. vomitoria is more variable than those known from mammalian and other invertebrate studies where, in those regulatory peptides containing a pair of adjacent prolyl residues so far studied, e.g., bradykinin, and the mosquito peptide Aea HP-I, only one of the pair (the second) is known to undergo hydroxylation. The truncated hexapeptide, des Gly-Pro Met-callatostatin could be produced as a result of the action of a dipeptidyl peptidase II type of enzyme which is known from mammalian studies to be unique in its ability to cleave between the two prolyl residues of an Xaa-Pro-Pro- sequence, where Xaa is any unprotected NH2-terminal amino acid. This enzyme is, however, considered unlikely to be able to cleave the Gly-Hyp-Pro-sequence, which would suggest a functional significance for such a post-translational modification. For this reason, it is of interest that [Hyp2]Met-callatostatin (and earlier, [Hyp3]Met-callatostatin) have been shown to be potent inhibitors of the spontaneous contractions of the hindgut of C. vomitoria (biphasic dose-response curve with IC50 values of 10(-14) M and 10(-7) M).(ABSTRACT TRUNCATED AT 250 WORDS)
D000595:Amino Acid Sequence; D000818:Animals; D004175:Diptera / Q000737:chemistry*; D005769:Gastrointestinal Motility / Q000502:physiology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification* / Q000378:metabolism* / Q000502:physiology; D010446:Peptide Fragments / Q000302:isolation & purification* / Q000502:physiology; D011499:Protein Processing, Post-Translational
C096416:Met-callatostatin; C096417:Met-callatostatin, Hyp(2)-; C096418:Met-callatostatin, des-Gly-des-Pro-; D009479:Neuropeptides; D010446:Peptide Fragments