The major virulence factor of Streptococcus pyogenes is M protein, an alpha-helical coiled-coil protein that shares structural homology with tropomyosin and myosin. It extends from the cell wall and prevents phagocytosis, inhibits complement binding, and mediates bacterial adherence. Antibodies against M protein form shortly after acute infection and may cross-react with epitopes on myosin, leading to rheumatic carditis.