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High affinity streptococcal binding to human fibronectin requires specific recognition of sequential F1 modules
Ulrich Schwarz-Linek1, Ewa S Pilka, Andrew R Pickford
1Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
The Journal of Biological Chemistry
|July 13, 2004
Summary
Streptococcus pyogenes uses SfbI protein to bind fibronectin (Fn), triggering bacterial entry into human cells. Specific Fn type 1 modules and SfbI motifs, in correct order, dictate this high-affinity interaction.
Area of Science:
- Microbiology
- Structural Biology
- Cell Biology
Background:
- * Streptococcus pyogenes internalization into human cells is mediated by fibronectin (Fn) binding to the SfbI protein.
- * This binding event triggers integrin-dependent pathogen entry into epithelial and endothelial cells.
Purpose of the Study:
- * To elucidate the structural basis for the specific and high-affinity interaction between Fn's N-terminal domain and SfbI.
- * To understand how Fn type 1 modules and SfbI motifs contribute to this binding.
Main Methods:
- * Nuclear magnetic resonance (NMR) spectroscopy.
- * Isothermal titration calorimetry (ITC).
- * Dissection approach to analyze molecular interactions.
Main Results:
- * All five Fn type 1 modules are involved in the interaction with SfbI.
- * Short, consecutive motifs within SfbI's repeat region recognize specific Fn modules.
- * The precise order of these SfbI motifs is critical for high-affinity binding to the Fn N-terminal domain.
Conclusions:
- * The study reveals the molecular basis for the specific and high-affinity binding between Streptococcus pyogenes SfbI and fibronectin.
- * Understanding this interaction is key to developing strategies against S. pyogenes infections.