M proteins are antigenically variable cell-surface virulence factors of group A Streptococcus (GAS). This organism is an important cause of human illness and notably provokes the autoimmune disease rheumatic fever. McNamara et al. examined a fragment of M1 that binds to host fibrinogen and promotes inflammation. The M1 protein consists of α-helical coiled coils bearing distinctive structural features that impart irregularity and instability to the coiled coil. These features mimic muscle myosin and tropomyosin, which may explain postinfection autoimmune responses. Mice immunized with a mutant, stabilized M protein exhibited reduced harmful inflammation without compromising protective immune responses.
C. McNamara, A. S. Zinkernagel, P. Macheboeuf, M. W. Cunningham, V. Nizet, P. Ghosh, Coiled-coil irregularities and instabilities in group A Streptococcus M1 are required for virulence. Science 319, 1405-1408 (2008). [Abstract] [Full Text]