Expression, purification and characterization of a catalytic domain of human protein tyrosine phosphatase non-receptor 12 (PTPN12) in Escherichia coli with FKBP-type PPIase as a chaperon

Protein Expr Purif. 2018 Feb:142:45-52. doi: 10.1016/j.pep.2017.09.014. Epub 2017 Sep 28.

Abstract

Protein tyrosine phosphatase non-receptor type 12 (PTPN12), also known as PTP-PEST, was broadly expressed in hemopoietic cells. Recent research has shown that this enzyme is involved in tumorigenesis, as well as in tumor progression and transfer, as it can suppress multiple oncogenic tyrosine kinases. However, the difficulty of soluble expression of PTP-PEST in prokaryotic cells has resulted in great limitations in investigating its structure and functions. In this study, we successfully carried out soluble expression of the catalytic domain of PTP-PEST (ΔPTP-PEST) in Escherichia coli and performed an enzymatic characterization and kinetics. To confirm expression efficiency, we also induced the expression of the chaperon, FKBP_C. FKBP_C expression indicated efficacious prokaryotic expression of ΔPTP-PEST. In conclusion, our work yielded a practical expression system and two-step chromatography purification method that may serve as a valuable tool for the structural and functional analysis of proteins that are difficult to express in the soluble form in prokaryotic cells.

Keywords: FKBP_C; PTP-PEST; PTPN12; Soluble expression; ΔPTP-PEST.

MeSH terms

  • Archaeal Proteins / genetics*
  • Archaeal Proteins / metabolism
  • Catalytic Domain
  • Cloning, Molecular
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Humans
  • Kinetics
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Peptidylprolyl Isomerase / genetics*
  • Peptidylprolyl Isomerase / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / isolation & purification
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12 / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tacrolimus Binding Proteins / genetics*
  • Tacrolimus Binding Proteins / metabolism
  • Thermococcus / chemistry*
  • Thermococcus / metabolism

Substances

  • Archaeal Proteins
  • Molecular Chaperones
  • Recombinant Fusion Proteins
  • PTPN12 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 12
  • Tacrolimus Binding Proteins
  • Peptidylprolyl Isomerase