Structure of a domain of protein A as a three-helix bundle binding to the heavy variable chain of a VH3 human Fab (left).[1] Minimized protein A bound to Fc fragment of Rituximab (right).[2] Uniprot P02976.
Identifiers
Symbol
SpA
Pfam
PF02216
InterPro
IPR003132
SCOP2
1DEE / SCOPe / SUPFAM
Available protein structures:
Pfam
structures / ECOD
PDB
RCSB PDB; PDBe; PDBj
PDBsum
structure summary
PDB
1dee, 1l6x
Protein A is a 42 kDa 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 is composed of five homologous Ig-binding domains that fold into a three-helix bundle. Each domain is able to bind proteins from many mammalian species, most notably IgGs. It binds the heavy chain within the Fc region of most immunoglobulins and also within the Fab region in the case of the human VH3 family. Through these interactions in serum, where IgG molecules are bound in the wrong orientation (in relation to normal antibody function), the bacteria disrupts opsonization and phagocytosis.[3]
^Graille M, Stura EA, Corper AL, Sutton BJ, Taussig MJ, Charbonnier JB, Silverman GJ (May 2000). "Crystal structure of a Staphylococcus aureus protein A domain complexed with the Fab fragment of a human IgM antibody: structural basis for recognition of B-cell receptors and superantigen activity". Proceedings of the National Academy of Sciences of the United States of America. 97 (10): 5399–404. Bibcode:2000PNAS...97.5399G. doi:10.1073/pnas.97.10.5399. PMC 25840. PMID 10805799.
^Idusogie EE, Presta LG, Gazzano-Santoro H, Totpal K, Wong PY, Ultsch M, et al. (April 2000). "Mapping of the C1q binding site on rituxan, a chimeric antibody with a human IgG1 Fc". Journal of Immunology. 164 (8): 4178–84. doi:10.4049/jimmunol.164.8.4178. PMID 10754313.
^Keener AB, Thurlow LT, Kang S, Spidale NA, Clarke SH, Cunnion KM, et al. (February 2017). "Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells". Journal of Immunology. 198 (3): 1263–1273. doi:10.4049/jimmunol.1600093. PMC 5266639. PMID 28031339.
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