Contributions of different modules of the plasminogen-binding Streptococcus pyogenes M-protein that mediate its functional dimerization.

•Group A S. pyogenes (GAS) is a causative agent in pharyngeal and dermal infections.•A major virulence determinant of GAS is the signature dimeric modular M-protein.•Host human plasminogen binds to the A-domain of all Pattern D M-proteins and governs virulence.•The determinants of Pattern D M-protein dimerization reside in its helical C-domain.•The modular nature of M-proteins are evolutionarily designed for bacterial survival in hostile host niches.