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Evolutionary and functional studies of protein H: a surface molecule of Streptococcus pyogenes

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Author

Summary, in English

Several bacterial species express surface proteins with affinity for the Fc part of human IgG. This thesis describes evolutionary and functional studies of protein H, an IgGFc-binding surface protein of the human pathogen Streptococcus pyogenes. By using peptide mapping and NMR analysis the IgGFc-binding region of protein G, a surface protein of group C and G streptococci, was identified. Various fragments of protein H localized the IgGFc-binding region to the N-terminal part of this molecule. It was also demonstrated that protein A, an IgGFc-binding protein of Staphylococcus aureus, protein G and protein H bind to the same site on IgGFc, although there is no sequence homology between the IgGFc-binding regions of these proteins. The finding that unrelated bacterial proteins have evolved regions with similar function, represents an example of convergent evolution. Protein H also absorbs albumin from human plasma and by using fragments of protein H, the albumin-binding region was mapped to the C-terminal part of the molecule. Protein G also binds albumin, and the albumin-binding regions of protein H and G show no sequence similarity, demonstrating that these regions also have evolved convergently. Protein H was found to interact with fibronectin type III (FNIII) domains, present in many eukaryotic proteins. The binding site was localized to the N-terminal part of protein H but did not overlap the binding site for IgG. Although the FNIII domain and the Ig-like domain have similar three-dimensional structure, protein H has evolved separate binding sites for these widespread domains. Many S. pyogenes strains aggregate when grown in vitro. Molecular analysis of this property in a strain expressing protein H, shows that protein H contributes to the aggregation. A 19 amino acids sequence was identified in the N-terminal part of protein H as responsible for the aggregation. Aggregating strains adhered to epithelial cells while isogenic mutants devoid of proteins containing the 19 a.a. sequence, did not. Soluble protein H binds to lymphocytes. It was shown that protein H is taken up by the lymphocytes and transported in to the nucleus via a previously unknown route. In the cytosol, protein H interacts with actin and nucleophosmin/B23, a shuttle protein between the cytoplasm and the nucleus. Within the nucleus protein H bind the nuclear proteins SET and hnRNP A2/B1, resulting in a cytostatic effect.

Publishing year

1998

Language

English

Document type

Dissertation

Publisher

Department of Cell and Molecular Biology, Lund University

Topic

  • Infectious Medicine

Keywords

  • intracellular transportation
  • adhesion
  • aggregation
  • FNIII domain
  • albumin-binding
  • M-like protein
  • convergent evolution
  • protein G
  • Streptococcus pyogenes
  • IgG-binding
  • Microbiology
  • bacteriology
  • virology
  • mycology
  • Mikrobiologi
  • bakteriologi
  • virologi
  • mykologi

Status

Published

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-2907-6
  • ISRN: LUMEDW/MECM--98/1014--SE

Defence date

8 May 1998

Defence time

10:15

Defence place

Lund

Opponent

  • Vincent Fischetti (Professor)