Replacement of domain b of human protein disulfide isomerase-related protein with domain b' of human protein disulfide isomerase dramatically increases its chaperone activity

FEBS Lett. 2004 May 21;566(1-3):311-5. doi: 10.1016/j.febslet.2004.03.103.

Abstract

We have reported that human protein disulfide isomerase-related protein (hPDIR) has isomerase and chaperone activities that are lower than those of the human protein disulfide isomerase (hPDI), and that the b domain of hPDIR is critical for its chaperone activity [J. Biol. Chem. 279 (2004) 4604]. To investigate the basis of the differences between hPDI and hPDIR, and to determine the functions of each hPDIR domain in detail, we constructed several hPDIR domain mutants. Interestingly, when the b domain of hPDIR was replaced with the b' domain of hPDI, a dramatic increase in chaperone activity that was close to that of hPDI itself was observed. However, this mutant showed decreased oxidative refolding of alpha1-antitrypsin. The replacement of the b domain of hPDIR with the c domain of hPDI also increased its chaperone activity. These observations suggest that putative peptide-binding sites of hPDI determine both its chaperone activity and its substrate specificity.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Humans
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Mutation
  • Oxidation-Reduction
  • Protein Disulfide-Isomerases / chemistry*
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrometry, Fluorescence

Substances

  • Molecular Chaperones
  • Proteins
  • Recombinant Proteins
  • PDIA5 protein, human
  • Protein Disulfide-Isomerases