One-step production of bioactive human lipopolysaccharide binding protein from LPS-eliminated E. coli

Protein Expr Purif. 2019 May:157:17-20. doi: 10.1016/j.pep.2019.01.008. Epub 2019 Jan 26.

Abstract

Human lipopolysaccharide (LPS) binding protein (LBP) is a ∼60 kDa glycosylated protein that mediates potent innate immune against invading Gram-negative bacteria by recognition of LPS in their outer membranes. To date, there is no method for efficient production of bioactive LPS-free LBP at sufficient amounts through prokaryotic expression system. Here we present a simple approach for rapid preparation of human LBP from a LPS-eliminated E. coli strain named ClearColi BL21 (DE)3. Combined with the usage of an ultra-high-affinity CL7/Im7 purification system, we achieved one-step purification of recombinant human LBP with over 90% purity at a yield of ∼4 mg/L when using LB culture medium. The produced LBP retains full LPS binding activity which was validated by fluorescence spectroscopy and isothermal titration calorimetry (ITC). Collectively, we develop a valid method that can be applied to cost-effectively produce and purify LPS-free proteins.

Keywords: E. coli ClearColi; Fluorescence spectroscopy; Isothermal titration calorimetry; Lipopolysaccharide binding protein; Ultra-high-affinity CL7/Im7 system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / genetics*
  • Acute-Phase Proteins / immunology
  • Acute-Phase Proteins / isolation & purification
  • Carrier Proteins / genetics*
  • Carrier Proteins / immunology
  • Carrier Proteins / isolation & purification
  • Cloning, Molecular / methods
  • Escherichia coli / genetics*
  • Genetic Vectors / genetics
  • Humans
  • Lipopolysaccharides / immunology*
  • Lipopolysaccharides / isolation & purification
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / isolation & purification
  • Plasmids / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology

Substances

  • Acute-Phase Proteins
  • Carrier Proteins
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Recombinant Proteins
  • lipopolysaccharide-binding protein