TY - JOUR
T1 - Cooperative binding and activation of fibronectin by a bacterial surface protein
AU - Marjenberg, Zoe R.
AU - Ellis, Ian R.
AU - Hagan, Robert M.
AU - Prabhakaran, Sabitha
AU - Höök, Magnus
AU - Talay, Susanne R.
AU - Potts, Jennifer R.
AU - Staunton, David
AU - Schwarz-Linek, Ulrich
PY - 2011/1/21
Y1 - 2011/1/21
N2 - 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 cellbased 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.
AB - 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 cellbased 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.
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U2 - 10.1074/jbc.M110.183053
DO - 10.1074/jbc.M110.183053
M3 - Article
C2 - 21059652
AN - SCOPUS:78751563801
VL - 286
SP - 1884
EP - 1894
JO - The Journal of biological chemistry
JF - The Journal of biological chemistry
SN - 0021-9258
IS - 3
ER -