The Solution and Crystal Structures of a Module Pair from the Staphylococcus aureus-Binding Site of Human Fibronectin—A Tale with a Twist

• Published in: Journal of molecular biology 2007-05, Vol.368 (3), p.833-844
• Main Authors: Rudiño-Piñera, Enrique, Ravelli, Raimond B.G., Sheldrick, George M., Nanao, Max H., Korostelev, Vladimir V., Werner, Joern M., Schwarz-Linek, Ulrich, Potts, Jennifer R., Garman, Elspeth F.
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Binding Sites; Carrier Proteins; crystallography; Crystallography, X-Ray; domain orientation; fibronectin; Fibronectins - chemistry; Fibronectins - metabolism; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; multidomains; NMR; Protein Structure, Secondary; Protein Structure, Tertiary; Solutions; Staphylococcus; Staphylococcus aureus - metabolism; Ultraviolet Rays
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2007.02.061

An important goal of structural studies of modular proteins is to determine the inter-module orientation, which often influences biological function. The N-terminal domain of human fibronectin (Fn) is composed of a string of five type 1 modules (F1). Despite their small size, to date F1 modules have proved intractable to X-ray structure solution, although there are several NMR structures available. Here, we present the first structures (two X-ray models and an NMR-derived model) of the 2F13F1 module pair, which forms part of the binding site for Fn-binding proteins from pathogenic bacteria. The crystallographic structure determination was aided by the novel technique of UV radiation damage-induced phasing. The individual module structures are very similar in all three models. In the NMR structure and one of the X-ray structures, a similar but smaller interdomain interface than that observed previously for 4F15F1 is seen. The other X-ray structure has a different interdomain orientation. This work underlines the benefits of combining X-ray and NMR data in the studies of multi-domain proteins.