Mass spectrometric identification of N- and O-glycosylation sites of full-length rat selenoprotein P and determination of selenide-sulfide and disulfide linkages in the shortest isoform

Biochemistry. 2003 Aug 19;42(32):9703-11. doi: 10.1021/bi0346300.

Abstract

Rat selenoprotein P is an extracellular glycoprotein of 366 amino acid residues that is rich in cysteine and selenocysteine. Plasma contains four isoforms that differ principally by length at the C-terminal end. Mass spectrometry was used to identify sites of glycosylation on the full-length protein. Of the potential N-glycosylation sites, three located at residues 64, 155, and 169 were occupied, while the two at residues 351 and 356 were not occupied. Threonine 346 was variably O-glycosylated. Thus, full-length selenoprotein P is both N- and O-glycosylated. The shortest isoform of selenoprotein P, which terminates at residue 244, was analyzed for selenide-sulfide and disulfide linkages. In this isoform, a single selenocysteine and seven cysteines are present. Mass spectrometric analysis indicated that a selenide-sulfide bond exists between Sec40 and Cys43. Two disulfides were also detected as Cys149-Cys167 and Cys153-Cys156. The finding of a selenide-sulfide bond in the shortest isoform is compatible with a redox function of this pair that might be analogous to the selenol-thiol pair near the C terminus of animal thioredoxin reductase. The disulfide formed by Cys153-Cys156 also has some characteristics of a redox active pair.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Carbohydrate Sequence
  • Disulfides / chemistry*
  • Glycosylation
  • Molecular Sequence Data
  • Peptide Fragments / analysis
  • Peptide Mapping
  • Protein Isoforms
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism
  • Rats
  • Selenium / chemistry*
  • Selenocysteine / chemistry
  • Selenoprotein P
  • Selenoproteins
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods
  • Sulfides / chemistry*

Substances

  • Disulfides
  • Peptide Fragments
  • Protein Isoforms
  • Proteins
  • Selenoprotein P
  • Selenoproteins
  • Sulfides
  • Selenocysteine
  • Selenium