Characterization of fibrinogen binding by glycoproteins Srr1 and Srr2 of Streptococcus agalactiae

Ho Seong Seo, George Minasov, Ravin Seepersaud, Kelly S. Doran, Ievgeniia Dubrovska, Ludmilla Shuvalova, Wayne F. Anderson, Tina M. Iverson, Paul M. Sullam*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The serine-rich repeat glycoproteins of Gram-positive bacteria comprise a large family of cell wall proteins. Streptococcus agalactiae (group B streptococcus, GBS) expresses either Srr1 or Srr2 on its surface, depending on the strain. Srr1 has recently been shown to bind fibrinogen, and this interaction contributes to the pathogenesis of GBS meningitis. Although strains expressing Srr2 appear to be hypervirulent, no ligand for this adhesin has been described. We now demonstrate that Srr2 also binds human fibrinogen and that this interaction promotes GBS attachment to endothelial cells. Recombinant Srr1 and Srr2 bound fibrinogen in vitro, with affinities of KD = 2.1 × 10-5 and 3.7 × 10-6M, respectively, as measured by surface plasmon resonance spectroscopy. The binding site for Srr1 and Srr2 was localized to tandem repeats 6-8 of the fibrinogen Aα chain. The structures of both the Srr1 and Srr2 binding regions were determined and, in combination with mutagenesis studies, suggest that both Srr1 and Srr2 interact with a segment of these repeats via a "dock, lock, and latch" mechanism. Moreover, properties of the latch region may account for the increased affinity between Srr2 and fibrinogen. Together, these studies identify how greater affinity of Srr2 for fibrinogen may contribute to the increased virulence associated with Srr2-expressing strains.

Original languageEnglish (US)
Pages (from-to)35982-35996
Number of pages15
JournalJournal of Biological Chemistry
Volume288
Issue number50
DOIs
StatePublished - Dec 13 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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