Antibacterial activity of glycosylated and phosphorylated chromogranin A-derived peptide 173-194 from bovine adrenal medullary chromaffin granules.
Recently, we have isolated from bovine chromaffin granules and identified two natural peptides possessing antibacterial activity: secretolytin (chromogranin B 614-626) and enkelytin (proenkephalin-A 209-237). Here, we characterize a large natural fragment, corresponding to chromogranin A 79-431, that inhibits growth of both Gram-positive and Gram-negative bacteria. The aim of the present work was to determine the shortest active peptide located in the 79-431 chromogranin A region. Three peptides, which shared the same 173-194 chromogranin A sequence (YPGPQAKEDSEGPSQGPASREK) but differed in post-translational modifications, including O-glycosylation and tyrosine phosphorylation, were isolated. A detailed study using microsequencing and mass spectrometry allowed us to correlate their antibacterial activity with these post-translational modifications. The chromogranin A precursor fragment (79-431) and the active glycosylated and phosphorylated peptides were, respectively, named prochromacin and chromacin (P, G, and PG for phosphorylated, glycosylated, and phosphorylated-glycosylated form).
Strub
J M
JM
INSERM, Unité 338 de Biologie de la Communication Cellulaire, Strasbourg, 67084 France.
Goumon
Y
Y
Lugardon
K
K
Capon
C
C
Lopez
M
M
Moniatte
M
M
Van Dorsselaer
A
A
Aunis
D
D
Metz-Boutigue
M H
MH
D000313:Adrenal Medulla / Q000737:chemistry*; D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D002837:Chromaffin Granules / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism* / Q000494:pharmacology; D006031:Glycosylation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D053379:Chromogranin A; D002864:Chromogranins; D010446:Peptide Fragments; C102362:chromogranin A (173-194)