The solution and crystal structures of a module pair from the Staphylococcus aureus-binding site of human fibronectin--a tale with a twist.
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.
Rudiño-Piñera
Enrique
E
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK.
Ravelli
Raimond B G
RB
Sheldrick
George M
GM
Nanao
Max H
MH
Korostelev
Vladimir V
VV
Werner
Joern M
JM
Schwarz-Linek
Ulrich
U
Potts
Jennifer R
JR
Garman
Elspeth F
EF
D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins; D018360:Crystallography, X-Ray; D005353:Fibronectins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions; D013211:Staphylococcus aureus / Q000378:metabolism*; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D012996:Solutions