Cooperative Binding and Activation of Fibronectin by a Bacterial Surface Protein

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

Research output: Contribution to journalArticlepeer-review

27 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
Early online date8 Nov 2010
DOIs
Publication statusPublished - 21 Jan 2011

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