Binding of Efb from Staphylococcus aureus to fibrinogen blocks neutrophil adherence

Ya Ping Ko, Xiaowen Liang, C. Wayne Smith, Jay L. Degen, Magnus Hook

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

In addition to its pivotal role in hemostasis, fibrinogen (Fg) and provisional fibrin matrices play important roles in inflammation and regulate innate immune responses by interacting with leukocytes. Efb (the extracellular fibrinogen-binding protein) is a secreted Staphylococcus aureus protein that engages host Fg and complement C3. However, the molecular details underlying the Efb-Fg interaction and the biological relevance of this interaction have not been determined. In the present study, we characterize the interaction of Efb with Fg. We demonstrate that the Fg binding activity is located within the intrinsically disordered N-terminal half of Efb (Efb-N) and that the D fragment of Fg is the region that mediates Efb-N binding. More detailed studies of the Efb-N-Fg interactions using ELISA and surface plasmon resonance analyses revealed that Efb-N exhibits a much higher affinity for Fg than typically observed with Fg-binding MSCRAMMs (microbial surface components recognizing adhesive matrix molecules), and data obtained from ELISA analyses using truncated Efb-N constructs demonstrate that Efb-N contains two binding sites located within residues 30-67 and 68-98, respectively. Efb-N inhibits neutrophil adhesion to immobilized Fg by binding to Fg and blocking the interaction of the protein with the leukocyte integrin receptor, αMβ 2. A motif in the Fg γ chain previously shown to be central to the αMβ2 interaction was shown to be functionally distinguishable from the Efb-N binding site, suggesting that the Fg-Efb interaction indirectly impedes Fg engagement by αMβ 2. Taken together, these studies provide insights into how Efb interacts with Fg and suggest that Efb may support bacterial virulence at least in part by impeding Fg-driven leukocyte adhesion events.

Original languageEnglish (US)
Pages (from-to)9865-9874
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number11
DOIs
StatePublished - Mar 18 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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