Identification and characterization of a novel secreted immunoglobulin binding protein from group A Streptococcus

Immunoglobulin binding proteins are one of several pathogenicity factors wh ich have been associated with invasive disease caused by group A streptococ ci. The surface-bound M and M-like proteins of Streptococcus pyogenes are t he most characterized of these immunoglobulin binding proteins, and in most cases they bind only a single antibody class. Here we report the identific ation of a novel non-M-type secreted protein, designated SibA (for secreted immunoglobulin binding protein from group A streptococcus), which binds al l immunoglobulin G (IgG) subclasses, the Fe and Fab fragments, and also IgA and IgM. SibA has no significant sequence homology to any M-related protei ns, is not found in the vir regulon, and contains none of the characteristi c M-protein regions, such as the A or C repeats. Like M proteins, however, SibA does have relatively high levels of alanine, lysine, glutamic acid, le ucine, and glycine. SibA and M proteins also share an alpha-helical N-termi nal secondary structure which has been previously implicated in immunoglobu lin binding in M proteins. Evidence presented here indicates that this is a lso the case for SibA. SibA also has regions of local similarity with other coiled-coil proteins such as Listeria monocytogenes P45 autolysin, human m yosin heavy chain, macrogolgin, and Schistoma mansoni paramyosin, some of w hich are of potential significance since cross-reactive antibodies between myosin proteins and M proteins have been implicated in the development of t he autoimmune sequelae of streptococcal disease.