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

TY - JOUR

T1 - The solution and crystal structures of a module pair from the Staphylococcus aureus-binding site of human fibronectin - A tale with a twist

AU - Rudino-Pinera, Enrique

AU - Ravelli, Raimond B. G.

AU - Sheldrick, George M.

AU - Nanao, Max H.

AU - Korostelev, Vladimir V.

AU - Werner, Joern M.

AU - Schwarz-Linek, Ulrich

AU - Potts, Jennifer R.

AU - Garman, Elspeth F.

PY - 2007/5/4

Y1 - 2007/5/4

N2 - 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 I 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. (c) 2007 Elsevier Ltd. All rights reserved.

AB - 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 I 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. (c) 2007 Elsevier Ltd. All rights reserved.

KW - fibronectin

KW - crystallography

KW - NMR

KW - multidomains

KW - domain orientation

KW - MACROMOLECULAR STRUCTURES

KW - MOLECULAR REPLACEMENT

KW - PLASMINOGEN-ACTIVATOR

KW - BACKBONE DYNAMICS

KW - DIPOLAR COUPLINGS

KW - GELATIN-BINDING

KW - GROWTH-FACTOR

KW - PROTEIN

KW - DOMAINS

KW - REFINEMENT

U2 - 10.1016/j.jmb.2007.02.061

DO - 10.1016/j.jmb.2007.02.061

M3 - Article

C2 - 17368672

SN - 0022-2836

VL - 368

SP - 833

EP - 844

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 3

ER -