Cooperative binding and activation of fibronectin by a bacterial surface protein.
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.
Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews KY16 9ST, Scotland, United Kingdom.
Zoe R
ZR
Marjenberg
Ian R
IR
Ellis
Robert M
RM
Hagan
Sabitha
S
Prabhakaran
Magnus
M
Höök
Susanne R
SR
Talay
Jennifer R
JR
Potts
David
D
Staunton
Ulrich
U
Schwarz-Linek
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D013297:Streptococcus pyogenes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D018829:Adhesins, Bacterial; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial