Structural and biochemical characterization of Staphylococcus aureus clumping factor B/ligand interactions

Area of Science:

• Microbiology
• Structural Biology
• Biochemistry

Background:

• Staphylococcus aureus colonization is linked to increased invasive disease risk.
• Clumping factor B (ClfB) is a key S. aureus virulence factor mediating nasal colonization.
• ClfB binds human cytokeratin 10 (K10) and fibrinogen (Fg), contributing to its role in infection.

Purpose of the Study:

• To determine the crystal structures of ClfB's ligand-binding region.
• To elucidate the binding mechanisms of ClfB with K10 and Fg.
• To understand the versatile ligand recognition of microbial surface components recognizing adhesive matrix molecules (MSCRAMM).

Main Methods:

• X-ray crystallography was used to determine the structures of ClfB.
• The study analyzed ClfB in apo-form and complexed with K10 and Fg α-chain peptides.
• Ligand-binding interactions were characterized at the molecular level.

Main Results:

• Crystal structures of ClfB in apo-form and bound to K10 and Fg peptides were determined.
• Both ligands bind ClfB via parallel β-sheet complementation, a conserved binding mode.
• A common GSSGXG motif in ligands is crucial for ClfB binding, suggesting potential for additional ligand interactions.

Conclusions:

• ClfB exhibits a versatile ligand recognition mode through β-sheet complementation.
• Specific residues in ClfB are critical for binding K10 and Fg.
• The identified GSSGXG motif implies ClfB may bind other human proteins, expanding its pathogenic potential.