Structural Studies on the Four Repetitive Fc-Binding Regions in Protein A from Staphylococcus aureus

Abstract

The covalent structures of the 4 highly homologous Fc-binding regions in protein A, regions D, A, B and C were 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 sequence of region B was elucidated by combining the results of Edman degradations on isolated fragment B peptides with the previously reported N[amino]-terminal sequence of the same fragment. Edman degradations of fragment 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 probable covalent structure for the N-terminal 27,000 MW portion of protein A responsible for the Ig[immunoglobulin]G-Fc-binding activities. It was not possible to assign the activities to specific structures within the regions. The sequence data indicate that mutual homology between the 4 regions and internal homologies within the regions exist. A stepwise gene fusion procedure was probably involved in the evolution of the protein.