Origin of polyproline-rich peptides in human butyrylcholinesterase tetramers

Chem Biol Interact. 2016 Nov 25;259(Pt B):63-69. doi: 10.1016/j.cbi.2016.02.007. Epub 2016 Feb 11.

Abstract

The human butyrylcholinesterase (HuBChE) tetramer is composed of 4 identical subunits and a noncovalently bound polyproline-rich peptide. In a previous report we identified lamellipodin as the source of the polyproline-rich peptides in HuBChE tetramers purified from plasma. Our current goal was to identify proteins in addition to lamellipodin that donate polyproline-rich peptides to plasma HuBChE tetramers. Peptides were released from 1 mg of pure plasma-derived HuBChE tetramers by boiling. Mass spectrometry identified 74 polyproline-rich peptides. MALDI-TOF mass spectra and spectral counting of the LC-MS/MS data supported the conclusion that lamellipodin accounted for 70% of the polyproline-rich peptides. Additional precursor proteins were matched through BLASTp searches, suggesting but not proving, that 20 proteins including UDP-N-acetyl glucosamine transferase ALG13 homolog, leiomodin 2, and zinc finger homeobox protein 2 are sources of polyproline-rich peptides found in HuBChE tetramers. Eighteen polyproline-rich peptides had no match in the human protein database. In conclusion, HuBChE assembles into tetramers through interaction of its C-terminal domain with polyproline peptides derived from a variety of proteins.

Keywords: Butyrylcholinesterase; Lamellipodin; Mass spectrometry; Polyproline; Tetramerization domain.

MeSH terms

  • Amino Acid Sequence
  • Butyrylcholinesterase / chemistry*
  • Butyrylcholinesterase / metabolism
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Chromatography, High Pressure Liquid
  • Databases, Protein
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Peptides / analysis*
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism
  • Protein Structure, Quaternary
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Peptides
  • Protein Precursors
  • RAPH1 protein, human
  • polyproline
  • Butyrylcholinesterase