Cooperative Binding and Activation of Fibronectin by a Bacterial Surface Protein

Zoe R. Marjenberg, Ian R. Ellis, Robert M. Hagan, Sabitha Prabhakaran, Magnus Hoeoek, Susanne R. Talay, Jennifer R. Potts, David Staunton, Ulrich Schwarz-Linek

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    24 Citations (Scopus)

    Abstract

    Integrin-dependent cell invasion of some pathogenic bacteria is mediated by surface proteins targeting the extracellular matrix protein fibronectin (FN). Although the structural basis for bacterial FN recognition is well understood, it has been unclear why proteins such as streptococcal SfbI contain several FN-binding sites. We used microcalorimetry to reveal cooperative binding of FN fragments to arrays of binding sites in SfbI. In combination with thermodynamic analyses, functional cell-based assays show that SfbI induces conformational changes in the N-terminal 100-kDa region of FN (FN100kDa), most likely by competition with intramolecular interactions defining an inactive state of FN100kDa. This study provides insights into how long range conformational changes resulting in FN activation may be triggered by bacterial pathogens.

    Original languageEnglish
    Pages (from-to)1884-1894
    Number of pages11
    JournalJournal of Biological Chemistry
    Volume286
    Issue number3
    DOIs
    Publication statusPublished - 21 Jan 2011

    Keywords

    • MIGRATION-STIMULATING FACTOR
    • STAPHYLOCOCCUS-AUREUS FNBPA
    • GROUP-A STREPTOCOCCI
    • TANDEM BETA-ZIPPER
    • EPITHELIAL-CELLS
    • GELATIN-BINDING
    • HOST-CELLS
    • PYOGENES
    • DOMAIN
    • ENTRY

    Cite this

    Marjenberg, Z. R., Ellis, I. R., Hagan, R. M., Prabhakaran, S., Hoeoek, M., Talay, S. R., Potts, J. R., Staunton, D., & Schwarz-Linek, U. (2011). Cooperative Binding and Activation of Fibronectin by a Bacterial Surface Protein. Journal of Biological Chemistry, 286(3), 1884-1894. https://doi.org/10.1074/jbc.M110.183053