Staphylococcus aureus Protein-A (SpA):

Protein A affinity chromatography has become well established as the preferred capture step for purification of human monoclonal IgG for in vivo applicaitons, so much so that it has become largely regarded as generic (Gagnon, “Polishing Methods ofr Monoclonal IgG Purification” chapter 17 in “process Scale Bioseparations for the Biopharmaceutical Industry”, p. 491). There are, however, some problems with Protein A chromatography. In order to elute the antibody, acidic conditions are required due to the high affinity of the antibodies to the resin. Explosure to these acidic conditions can result in the formation of protein aggregates. Some strategies to address aggregation include a additional chromatography steps or to use stabilizing agents (this has a problem itself in that these stabilizing agents must now be purified) (Chmielowski (US13/058301).  

It is well established that immunoglobulin binding proteins interact with a number of distinct epitopes on teh full lenght antibody and this adds to their functioanl flexiblity. Protein L binds to the Vl of Kappa light chains, Protein M interacts through conserved framework regions on the VL and Vk and binds both isotpyes with high affinity (low nM). Proteins A and G are multi-specific prtoeins possessing binding affinity to the Fc as well as the Fab protion of teh antibody. Each binds to the hinge region connecting CH2 and CH3 on teh Fc protion of teh IgG with high affinity. Additionally, Protein binds to the VH3 subset of VH domains which includes about 30-50% of the circulating IgGs. Protein G binds to the constant domain of teh Fab porition of IgG through its interction with teh CH1 domain, a highly conserved domain across many isotypes and species. (Baily, J of Immunological Methods, 415 (2014) 24-30). 

Multiple Binding Domains of SpA: (see multimers of SpA domains under “Affinity Chromatography”)