A ‘Collagen Hug’ Model for Staphylococcus aureus CNA binding to collagen

• Published in: The EMBO journal Vol. 24; no. 24; pp. 4224 - 4236
• Main Authors: Zong, Yinong, Xu, Yi, Liang, Xiaowen, Keene, Douglas R, Höök, Agneta, Gurusiddappa, Shivasankarappa, Höök, Magnus, Narayana, Sthanam V L
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 21.12.2005; Blackwell Publishing Ltd; Nature Publishing Group
• Subjects: Adhesins, Bacterial - chemistry; Adhesins, Bacterial - metabolism; bacterial adhesion; Collagen - chemistry; collagen binding; Crystallography, X-Ray; DNA - chemistry; Dose-Response Relationship, Drug; Extracellular Matrix - chemistry; Immunoglobulin G - chemistry; Ligands; Models, Biological; Models, Molecular; Peptides - chemistry; Polymerase Chain Reaction; Protein Binding; Protein Folding; Protein Structure, Secondary; Protein Structure, Tertiary; protein–protein; Staphylococcus aureus; Staphylococcus aureus - metabolism; Surface Plasmon Resonance; surface proteins
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/sj.emboj.7600888

The structural basis for the association of eukaryotic and prokaryotic protein receptors and their triple‐helical collagen ligand remains poorly understood. Here, we present the crystal structures of a high affinity subsegment of the Staphylococcus aureus collagen‐binding CNA as an apo‐protein and in complex with a synthetic collagen‐like triple helical peptide. The apo‐protein structure is composed of two subdomains (N1 and N2), each adopting a variant IgG‐fold, and a long linker that connects N1 and N2. The structure is stabilized by hydrophobic inter‐domain interactions and by the N2 C‐terminal extension that complements a β‐sheet on N1. In the ligand complex, the collagen‐like peptide penetrates through a spherical hole formed by the two subdomains and the N1–N2 linker. Based on these two structures we propose a dynamic, multistep binding model, called the ‘Collagen Hug’ that is uniquely designed to allow multidomain collagen binding proteins to bind their extended rope‐like ligand.