A 'Collagen Hug' model for Staphylococcus aureus CNA binding to collagen

Area of Science:

• Structural biology
• Microbiology
• Biochemistry

Background:

• The interaction between protein receptors and collagen is crucial in both eukaryotic and prokaryotic systems but remains structurally undefined.
• Understanding these interactions is vital for deciphering pathogen adhesion mechanisms and host-matrix interactions.

Purpose of the Study:

• To determine the structural basis of the collagen-binding mechanism of Staphylococcus aureus CNA.
• To elucidate the interaction between CNA and its triple-helical collagen ligand.

Main Methods:

• X-ray crystallography was employed to determine the structures of the Staphylococcus aureus collagen-binding protein (CNA) in its apo form and complexed with a synthetic collagen-like peptide.
• Structural analysis focused on the protein's subdomains, linker regions, and the mode of ligand binding.

Main Results:

• The apo-CNA structure reveals two subdomains (N1 and N2) with variant IgG-folds, connected by a linker, stabilized by hydrophobic interactions and an N2 C-terminal extension.
• In complex with the collagen-like peptide, the ligand occupies a spherical cavity formed by the N1 and N2 subdomains and the linker.
• A dynamic, multistep binding model, termed the 'Collagen Hug,' is proposed, explaining how multidomain proteins bind extended collagen ligands.

Conclusions:

• The crystal structures provide unprecedented insight into the molecular mechanism of collagen binding by Staphylococcus aureus CNA.
• The proposed 'Collagen Hug' model offers a framework for understanding collagen recognition by related multidomain proteins.
• This structural understanding may inform the development of novel therapeutic strategies targeting bacterial adhesion.