An efficient system for small protein expression and refolding

Biochem Biophys Res Commun. 2004 Apr 30;317(2):401-5. doi: 10.1016/j.bbrc.2004.03.068.

Abstract

The low expression yield and poor refolding efficiency of small recombinant proteins expressed in Escherichia coli have continued to hinder the large-scale purification of such proteins for structural and biological investigations. A system based on a small fusion partner, the B1 domain of Streptococcal protein G (GB1), was utilized to overcome this problem. We have tested this system on a small cysteine-rich toxin, mutant myotoxin alpha (MyoP20G). The highly expressed fusion protein was refolded using an unfolding/refolding protocol. Due to the small size of GB1, we were able to monitor the unfolding/refolding status by heteronuclear single quantum coherence (HSQC) NMR spectroscopy. The final product yielded well-resolved NMR spectra, with a topology corresponding to the natural product. We conclude that GB1 not only increases the expression level but also enhances the refolding of small proteins.

Publication types

  • Evaluation Study

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Crotalid Venoms / genetics
  • Crotalid Venoms / metabolism*
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism*
  • Feasibility Studies
  • Gene Expression Regulation, Bacterial / physiology
  • Gene Transfer Techniques*
  • Genetic Enhancement / methods*
  • Magnetic Resonance Spectroscopy
  • Molecular Weight
  • Protein Engineering / methods*
  • Protein Folding
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / chemistry

Substances

  • Bacterial Proteins
  • Crotalid Venoms
  • IgG Fc-binding protein, Streptococcus
  • Recombinant Fusion Proteins
  • myotoxin A