Molecular modification of Protein A to improve the elution pH and alkali resistance in affinity chromatography

Appl Biochem Biotechnol. 2014 Apr;172(8):4002-12. doi: 10.1007/s12010-014-0818-1. Epub 2014 Mar 6.

Abstract

Protein A of Staphylococcus aureus has been widely used as an affinity ligand for the purification of immunoglobulin. However, the low elution pH and the sensitivity to alkaline condition restricted the large-scale application of antibody purification. To overcome these disadvantages, the B domain was selected and mutated to Z domain and the recombinant Protein A was reconstructed by linking five Z domains. First, a section of six glycines was inserted into the second loop of Z domain, Z (6G). This increased the elution pH to 4.0-5.0. Then, the site-specific mutagenesis was conducted by replacing the 23rd asparagines to threonine and 30th phenylalanine to alanine, Z (N23T, F30A). These mutations made the recombinant Protein A shown a higher alkaline resistance than the nature Protein A. The work confirmed the modification of Protein A and exhibited the characteristics of recombinant Staphylococcal Protein A for antibody purification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Alkalies / pharmacology
  • Amino Acid Sequence
  • Animals
  • Cattle
  • Chromatography, Affinity*
  • Hydrogen-Ion Concentration
  • Immunoglobulin G / isolation & purification
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Protein Engineering / methods*
  • Protein Stability
  • Protein Structure, Tertiary
  • Staphylococcal Protein A / chemistry*
  • Staphylococcal Protein A / genetics*

Substances

  • Alkalies
  • Immunoglobulin G
  • Staphylococcal Protein A