title: Post-translational amino acid racemization in the frog skin peptide deltorphin I in the secretion granules of cutaneous serous glands.
abstract: The dermal glands of the South American hylid frog Phyllomedusa bicolor synthesize and expel huge amounts of cationic, alpha-helical, 24- to 33-residue antimicrobial peptides, the dermaseptins B. These glands also produce a wide array of peptides that are similar to mammalian hormones and neuropeptides, including a heptapeptide opioid containing a D-amino acid, deltorphin I (Tyr-DAla-Phe-Asp-Val-Val-Gly NH2). Its biological activity is due to the racemization of L-Ala2 to D-Ala. The dermaseptins B and deltorphins are all derived from a single family of precursor polypeptides that have an N-terminal preprosequence that is remarkably well conserved, although the progenitor sequences giving rise to mature opioid or antimicrobial peptides are markedly different. Monoclonal and polyclonal antibodies were used to examine the cellular and ultrastructural distributions of deltorphin I and dermaseptin B in the serous glands by immunofluoresence confocal microscopy and immunogold-electron microscopy. Preprodeltorphin I and preprodermaseptins B are sorted into the regulated pathway of secretion, where they are processed to give the mature products. Deltorphin I, [l-Ala2]-deltorphin I and dermaseptin B are all stored together in secretion granules which accumulate in the cytoplasm of all serous glands. We conclude that the L- to D-amino acid isomerization of the deltorphin I occurs in the secretory granules as a post-translational event. Thus the specificity of isomerization depends on the presence of structural and/or conformational determinants in the peptide N-terminus surrounding the isomerization site.
authors.affiliation: Peptidome de la peau d'amphibiens, FRE 2852, CNRS-Université Paris-6, Tour 43, Institut Jacques Monod, 2 Place Jussieu, F-75251 Paris, Cedex 05, France.
authors.forename: Constance
authors.initials: C
authors.lastname: Auvynet
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
authors.forename: Irene
authors.initials: I
authors.lastname: Dunia
authors.forename: Pierre
authors.initials: P
authors.lastname: Nicolas
authors.forename: Mohamed
authors.initials: M
authors.lastname: Amiche
authors.forename: Claire
authors.initials: C
authors.lastname: Lacombe
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D029845:Amphibian Proteins / Q000737:chemistry; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry; D001001:Anura / Q000378:metabolism*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D022142:Secretory Vesicles / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000596:Amino Acids; D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D009842:Oligopeptides; C059567:deltorphin; C060208:deltorphin I, Ala(2)-; C070905:dermaseptin