Temperature-dependent structure and function of group A streptococcal M proteins

University dissertation from Tommy Cedervall, Nobelvägen 60F, 214 33 MALMÖ, Sweden

Abstract: Temperature-dependent structure and function of group A streptococcal M proteins.This thesis describes the temperature-dependent structure of the members in the group A streptococcal M protein family. M proteins are cell-surface proteins that are important for the bacterial virulence and bind to a diverse set of human plasma proteins. The proteins are dimeric coiled-coil molecules, but temperature unstable, i.e. at 37°C the isolated proteins are monomeric molecules and to a great extent unfolded. It was shown that the Ig-binding by group A streptococcal strains was weaker at 37°C than 20°C. The Ig-binding by isolated M proteins and M-like proteins was, likewise, weaker at 37°C than 20°C. In contrast, the fibrinogen-binding by bacteria was equally strong at 20°C and 37°C, while the fibrinogen-binding by isolated protein was temperature-dependent. The M protein can be divided into class A and C proteins depending on whether centrally located repeats are A- or C-repeats. The coiled-coil structure of a fibrinogen-binding class A protein, Mrp4, was found to be temperature stable with strong fibrinogen-binding also at 37°C. The class A proteins have a higher percentage of hydrophobic amino acids in residues constituting the hydrophobic core in coiled-coil proteins than class C proteins. This disparity was suggested to explain the different temperature stabilities in class A and C proteins. The temperature stability also varies among class C proteins and higher temperature stability is accompanied by higher percentage hydrophobic amino acids in the hydrophobic core. The unfolding of M proteins indicated one to three structural regions. Furthermore, near-UV circular dichroism studies indicated a lower temperature stability of the N-terminal half of protein H, a class C proteins, compared to the overall helical structure. In opposite, the binding of IgG by protein H stabilised the N-terminal half to a higher extent than the overall helical structure.

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