Cooperative binding and activation of fibronectin by a bacterial surface protein

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 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.

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 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.

KW - Adhesins, Bacterial

KW - Binding Sites

KW - Cells, Cultured

KW - Fibroblasts

KW - Fibronectins

KW - Humans

KW - Protein Binding

KW - Streptococcus pyogenes

UR - http://www.scopus.com/inward/record.url?scp=78751563801&partnerID=8YFLogxK

U2 - 10.1074/jbc.M110.183053

DO - 10.1074/jbc.M110.183053

M3 - Article

C2 - 21059652

SN - 1083-351X

VL - 286

SP - 1884

EP - 1894

JO - The Journal of biological chemistry

JF - The Journal of biological chemistry

IS - 3

ER -