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The Nonideal Coiled Coil of M Protein and Its Multifarious Functions in Pathogenesis

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 715)

Abstract

The M protein is a major virulence factor of Streptococcus pyogenes (group A Streptococcus, GAS). This gram-positive bacterial pathogen is responsible for mild infections, such as pharyngitis, and severe invasive disease, like streptococcal toxic shock syndrome. M protein contributes to GAS virulence in multifarious ways, including blocking deposition of antibodies and complement, helping formation of microcolonies, neutralizing antimicrobial peptides, and triggering a proinflammatory and procoagulatory state. These functions are specified by interactions between M protein and many host components, especially C4BP and fibrinogen. The former interaction is conserved among many antigenically variant M protein types but occurs in a strikingly sequence-independent manner, and the latter is associated in the M1 protein type with severe invasive disease. Remarkably for a protein of such diverse interactions, the M protein has a relatively simple but nonideal α-helical coiled coil sequence. This sequence nonideality is a crucial feature of M protein. Nonideal residues give rise to specific irregularities in its coiled-coil structure, which are essential for interactions with fibrinogen and establishment of a proinflammatory state. In addition, these structural irregularities are reminiscent of those in myosin and tropomyosin, which are targets for crossreactive antibodies in patients suffering from autoimmune sequelae of GAS infection.

Keywords

  • Necrotizing Fasciitis
  • Coiled Coil
  • Acute Rheumatic Fever
  • Streptococcal Toxic Shock Syndrome
  • Heparin Binding Protein

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Fig. 12.1
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Ghosh, P. (2011). The Nonideal Coiled Coil of M Protein and Its Multifarious Functions in Pathogenesis. In: Linke, D., Goldman, A. (eds) Bacterial Adhesion. Advances in Experimental Medicine and Biology, vol 715. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0940-9_12

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