Differential expression of the Ebola virus GP(1,2) protein and its fragments in E. coli

Protein Expr Purif. 2007 Jul;54(1):117-25. doi: 10.1016/j.pep.2007.02.004. Epub 2007 Feb 15.

Abstract

Bacterial expression platforms are frequently used for the expression and production of different recombinant proteins. The full length Ebola virus (EBOV) GP(1,2) gene and subfragments of the GP(1) gene were cloned in a bacterial expression vector as a C-terminal His(6) fusion protein. Surprisingly, the full length EBOV GP(1,2) gene could not be expressed in Escherichia coli. The subfragments of GP(1) were only expressed in small amounts with the exception of one small fragment (subfragment D) which was expressed at very high levels as inclusion bodies. This was seen even in the in vitro translation system with no expression of full length GP(1,2), GP(1) subfragments A and C and low level expression of subfragment B. Only the subfragment D showed high level of expression. In E. coli (Top10), the recombinant GP(1) subfragment D protein was expressed exclusively as an insoluble approximately 25 kDa His(6) fusion protein, which is the expected size for a non-glycosylated recombinant protein. The IMAC purified and refolded non-glycosylated protein was used to immunize mice for the development of monoclonal anti-EBOV antibodies which successfully yielded several monoclonal antibodies with different specificities. The monoclonal and polyclonal antiserum derived from the animals immunized with this recombinant GP(1) subfragment D protein was found to specifically recognize the full length glycosylated EBOV GP(1,2) protein expressed in mammalian 293T cells, thus, demonstrating the immunogenicity of the recombinant subfragment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromatography, Affinity
  • Cloning, Molecular / methods*
  • Escherichia coli / genetics
  • Humans
  • Hybridomas
  • Immunization
  • Mice
  • Peptide Fragments / biosynthesis*
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Protein Folding
  • Recombinant Fusion Proteins / biosynthesis*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / isolation & purification
  • Viral Envelope Proteins / biosynthesis*
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / genetics

Substances

  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • envelope glycoprotein, Ebola virus