Structural characterization by mass spectrometry of native and recombinant human relaxin

Biomed Environ Mass Spectrom. 1990 Nov;19(11):655-64. doi: 10.1002/bms.1200191105.

Abstract

Mass spectrometry has played a key role in characterizing the primary structure of native and recombinant relaxin, a peptide hormone that induces ripening of the cervix prior to childbirth. The peptide is composed of two chains, A and B, and is formed from a single-chain prohormone, as is insulin. Aside from conserved cysteines, though, it has little sequence homology with insulin. Due to the small amounts of native peptide initially available (less than 10 pmol), traditional techniques could not provide information on the blocked A-chain sequence, on the carboxyterminal sequences, nor on other possible post-translational modifications. Mass measurements by fast atom bombardment (FAB) were made on reduced human relaxin isolated from corpora lutea. The detection limit by FAB for reduced relaxin was 500 fmol. The B-chain was four amino acids shorter than expected from comparison of the previously known cDNA sequence with homologous rat and porcine sequences. The A-chain, as predicted, was 24 amino acids in length and had a pyroglutamic acid residue on the amino-terminus. The purified samples were homogeneous with no other post-translational modifications. The recombinant relaxin molecule was also extensively characterized by mass spectrometry. In addition to the intact molecule, all tryptic peptides were characterized by FAB. A capillary high-performance liquid chromatography continuous-flow FAB system, developed for high-sensitivity peptide mapping, aided in these analyses. Finally, the three disulfide bonds were shown by tandem mass spectrometry to match those of insulin.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatography, High Pressure Liquid
  • Corpus Luteum / chemistry
  • Disulfides / analysis
  • Female
  • Humans
  • Hydrolysis
  • Male
  • Mass Spectrometry
  • Molecular Sequence Data
  • Peptide Fragments / analysis
  • Recombinant Proteins / analysis
  • Relaxin / analysis*
  • Relaxin / genetics
  • Spectrophotometry, Ultraviolet
  • Swine
  • Trypsin

Substances

  • Disulfides
  • Peptide Fragments
  • Recombinant Proteins
  • Relaxin
  • Trypsin