Protein A


Protein A

Protein A is a 40-60 kDa MSCRAMM surface protein originally found in the cell wall of the bacteria "Staphylococcus aureus". It is encoded by the "spa" gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical research because of its ability to bind immunoglobulins. It binds proteins from many of mammalian species, most notably IgG’s. It binds with the Fc region of immunoglobulins through interaction with the heavy chain. The result of this type of interaction is that, in serum, the bacteria will bind IgG molecules in the wrong orientation (in relation to normal antibody function) on their surface which disrupts opsonization and phagocytosis.

Protein A antibody binding

It binds with high affinity to human IgG1 and IgG2 as well as mouse IgG2a and IgG2b. Protein A binds with moderate affinity to human IgM, IgA and IgE as well as to mouse IgG3 and IgG1. [http://www1.gelifesciences.com/aptrix/upp00919.nsf/Content/AC7760572A5CE500C125702800083FED/$file/11003558AA.pdf] It does not react with human IgG3 or IgD, nor will it react to mouse IgM, IgA or IgE.

Other antibody binding proteins

In addition to Protein A, other immunoglobulin-binding bacterial proteins such as Protein G, Protein A/G and Protein L are all commonly used to purify, immobilize or detect immunoglobulins. Each of these immunoglobulin-binding proteins has a different antibody binding profile in terms of the portion of the antibody that is recognized and the species and type of antibodies it will bind.

Role in pathogenesis

As a pathogen "Staphylococcus aureus" utilizes Protein A, along with a host of other proteins and surface factors to aid its survival and, thus, virulence. Protein A helps inhibit phagocytic engulfment and acts as an immunological disguise. Mutants of "S. aureus" lacking protein A are more efficiently phagocytosed in vitro, and mutants in infection models have diminished virulence.

Recent research has also shown that Protein A is especially excellent at killing the B lymphocytes now believed to be central to the immune system defense from bacterial infections like staph (reference?). This may prove to eventually be of some pharmaceutical use. It is these same B cells can be a source in other people of crippling diseases like rheumatoid arthritis and lupus, so this could lead to new therapies to suppress responses that are the cause of autoimmune diseases. [Goodyear CS and Silverman GJ. Death by a B-cell superantigen: In vivo VH targeted apoptotic supra-clonal B-cell deletion by a staphylococcal toxin. J. Exp. Med. 2003 197: 1125-1139.]

Research

Recombinant Staphylococcal Protein A is often produced in "E. coli" for use in immunology and other biological research. One recombinant form of Protein A is called MabSelect.Protein A is often coupled to other molecules such as a fluorescent dye, enzymes, biotin, colloidal gold or radioactive iodine without affecting the antibody binding site. It is also widely utilized coupled to magnetic, latex and agarose beads.

Protein A is often immobilized onto a solid support and used as reliable method for purifying total IgG from crude protein mixtures such as serum or ascites fluid, or coupled with one of the above markers to detect the presence of antibodies. Immunoprecipitation studies with protein A conjugated to beads are also commonly used to purify proteins or protein complexes indirectly through antibodies against the protein or protein complex of interest.

References

2. Fournier, B and Klier A. 2004. Protein A gene expression is regulated by DNA supercoiling which is modified by the ArlS-ArlR two-component system of "Staphylococcus aureus". "Microbiology" 150, 3807-3819.


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