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

J Mol Biol. 2007 May 4;368(3):833-44. doi: 10.1016/j.jmb.2007.02.061. Epub 2007 Feb 22.

Abstract

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.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Carrier Proteins
  • Crystallography, X-Ray
  • Fibronectins / chemistry*
  • Fibronectins / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Solutions
  • Staphylococcus aureus / metabolism*
  • Ultraviolet Rays

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Fibronectins
  • Solutions

Associated data

  • PDB/2CG6
  • PDB/2CG7
  • PDB/2CKU