Structural studies on the four repetitive Fc-binding regions in protein A from Staphylococcus aureus.

The convalent structures of the four highly homologous Fc-binding regions in protein A, regions D, A, B, and C, have been studied by enzymic fragmentations of previously isolated fragments originating from these regions and subsequent isolation of the generated peptides by ion-exchange chromatography, molecular-sieve chromatography, high-voltage paper electrophoresis and paper chromatography. The complete seqeunce of region B was elucidated by combining the results of Edman degradations on isolated fragment B peptides with the previously reported N-terminal seqeunce of the same fragment. Furthermore, Edman degradations of fragments D, A and C peptides differing from the region B sequence provided the structures of subregions not identical to corresponding subregions within region B. Thus, it is possible to propose a highly probably covalent structure for the N-terminal 27000-molecular-weight portion of protein A responsible for the IgG-Fc-binding activities. However, it was not possible to assign the activities to specific structures within the regions. The sequence data indicate that not only mutual homology between the four regions exists, but also internal homologies within the regions. Furthermore, the data strongly supports the hypothesis of a stepwise gene fusion procedure being involved in the evolution of the protein.