Structural Similarities between M Protein and Tropomyosin

M proteins of the group A streptococcus, despite their well-recognized immunological variations, have the unique capacity of maintaining a common antiphagocytic function for the organism. Antibodies to M proteins, however, are capable of neutralizing the antiphagocytic activity of these molecules (1-3). Although, immunological cross-reactions between different M types have been observed (4-6), the opsonic activity of the M antibody is type specific (4, 7). Rarely does an antibody opsonic to one M type serve the same function for another. In an at tempt to understand the structural features governing the common biological function of the immunologically diverse M proteins, we have undertaken studies on the pr imary structure of these molecules. Our previous work (8) on the comparison of the partial sequence of M5 protein with M24, the only other M protein for which partial sequences have been reported (9), revealed certain similarities between them. In the present paper, we report the partial sequence of a third M protein; namely, M6, and additional sequence data on the M5 molecule. Comparison of these partial sequences with those of the M24 molecule (9) indicated that despite sequence variations certain amino acid identities were common to the three M molecules, which suggests a conservative sequence relationship between these proteins. In addition, secondary structural analysis of these known M protein segments revealed that they all exhibit high alpha-helical potential. Even more striking was the fact that they all contained regions exhibiting a repeating seven residue periodicity. Furthermore, the amino acid identities common to the homologous regions of the three M proteins occupied defined positions within the seven residue period. In a recent report from our laboratory (10), we indicated that M protein has a close physicochemical resemblance to mammal ian muscle tropomyosin. An examination of the partial sequence of the M24 protein (9) revealed significant similarity between this bacterial stz:face molecule and segments of mammal ian muscle tropomyosin with up to 40% identical residues. In the present report, we have compared the partial sequence of two additional M molecules (M5 and M6) with tropomyosin to determine if the similarities observed with the M24 protein are a general feature of the M molecules. The results of these studies indicate that M5 and M6 proteins reveal even