Group A streptococcal (GAS) M proteins are key determinants of virulence and pathogenicity. The high sequence diversity of M proteins has obvious implications for interactions of GAS with their host. However, there is only limited understanding of how M protein sequences and their multifarious functions are related. Structural analyses of M proteins and their molecular complexes can fill in this gap in knowledge. We solved high-resolution crystal structures of the hypervariable region of the M3 protein, which adopts a unique fold that deviates from the linear dimeric coiled-coil structure generally assumed for M proteins. Structures of M3:collagen peptide complexes reveal the molecular basis for promiscuous high-affinity binding of M3 to collagens, which might play an important role in GAS virulence and rheumatic fever pathogenesis.