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

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Bacterial Adhesion

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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  1. Department of Chemistry and Biochemistry, University of California, San Diego, CA, 92093-0375, USA

    Partho Ghosh

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Correspondence to Partho Ghosh .

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  1. , Department I, Protein Evolution, Max-Planck Institute for Developmental B, Spemannstr. 35, Tübingen, 72076, Germany

    Dirk Linke

  2. , Institute of Biotechnology, University of Helsinki, Viikinkaari 1, Helsinki, FIN-00014, Finland

    Adrian Goldman

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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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