The solution and crystal structures of a module pair from the Staphylococcus aureus-binding site of human fibronectin--a tale with a twist.

Journal article

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 (2)F1(3)F1 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 (4)F1(5)F1 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.

Authors: Rudiño-Piñera, E; Ravelli, R; Sheldrick, G; Nanao, M; Korostelev, V

• Publication status: Published
• Journal: Journal of molecular biology
• Volume: 368
• Issue: 3
• Pages: 833-844
• Publication date: 2007-05-01
• DOI: 10.1016/j.jmb.2007.02.061
• EISSN: 1089-8638
• ISSN: 0022-2836
• Language: English
• Keywords: Protein Structure, Secondary; Models, Molecular; Protein Structure, Tertiary; Binding Sites; Bacterial Proteins; Fibronectins; Crystallography, X-Ray; Carrier Proteins; Staphylococcus aureus; Solutions; Magnetic Resonance Spectroscopy; Humans; Ultraviolet Rays