Post-translational modification of bovine pro-opiomelanocortin. Tyrosine sulfation and pyroglutamate formation, a mass spectrometric study

J Biol Chem. 1990 Dec 25;265(36):22130-6.

Abstract

The amino-terminal fragment of beta-lipotropin (i.e. beta-lipotropin (1-40)) and joining peptide portions of pro-opiomelanocortin have been purified from extracts of bovine posterior pituitaries. Peptides were purified using a combination of reversed-phase and ion-exchange batch extraction procedures followed by reversed-phase high performance liquid chromatography. beta-Lipotropin (1-40) was found to consist of four major components while joining peptide was found to consist of two major components. Fast atom bombardment-mass spectrometric analysis of the tryptic fragments of both peptides revealed that the observed heterogeneity could be explained in terms of post-translational modifications. beta-Lipotropin (1-40) was found to be sulfated at tyrosine residue 28 to an extent of about 50%. The tyrosine residue in beta-lipotropin (1-40) is situated within an amino acid sequence with a preponderance of glutamate residues. Sulfation of this amino acid residue is entirely compatible with the known primary structure requirements of the sulfotransferase enzyme located in the trans-Golgi fraction. Both beta-lipotropin (1-40) and joining peptide were found to have pyroglutamate at their amino termini to an extent of about 50%. The cDNA sequence for bovine pro-opiomelanocortin predicts the presence of glutamic acid at position 1 of both peptides. Pyroglutamate is normally formed through the cyclization of glutamine. This reaction is thought to be catalyzed by a pyroglutamate forming enzyme located within the secretory granule fraction. Under certain circumstances peptides with glutamate at their amino termini may act as substrates for this enzyme.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Chromatography, High Pressure Liquid
  • Mass Spectrometry / methods
  • Molecular Sequence Data
  • Peptide Fragments / isolation & purification
  • Pro-Opiomelanocortin / chemistry
  • Pro-Opiomelanocortin / genetics*
  • Protein Processing, Post-Translational*
  • Pyrrolidonecarboxylic Acid / analysis*
  • Sulfates / analysis
  • Tyrosine*
  • beta-Lipotropin / chemistry
  • beta-Lipotropin / genetics*

Substances

  • Peptide Fragments
  • Sulfates
  • Tyrosine
  • Pro-Opiomelanocortin
  • beta-Lipotropin
  • Pyrrolidonecarboxylic Acid

Grants and funding