Norris, Nicole C, Bingham, Richard, Harris, Gemma, Speakman, Adrian, Jones, Richard P O, Leech, Andrew, Turkenburg, Johan P and Potts, Jennifer R (2011) Structural and functional analysis of the tandem β-zipper interaction of a streptococcal protein with human fibronectin. The Journal of biological chemistry, 286 (44). pp. 38311-38320. ISSN 1083-351X
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Bacterial fibronectin-binding proteins (FnBPs) contain a large intrinsically-disordered region (IDR) that mediates adhesion of bacteria to host tissues, and invasion of host cells, through binding to fibronectin (Fn). These FnBP IDRs consist of Fn-binding repeats (FnBRs) that form a highly extended tandem β-zipper interaction on binding to the N-terminal domain of Fn. Several FnBR residues are highly conserved across bacterial species, and here we investigate their contribution to the interaction. Mutation of these residues to alanine in SfbI-5 (a disordered FnBR from the human pathogen Streptococcus pyogenes) reduced binding but for each residue the change in free energy of binding was <2 kcal/mol. The structure of an SfbI-5 peptide in complex with the second and third F1 modules from Fn confirms that the conserved FnBR residues play equivalent functional roles across bacterial species. Thus, in SfbI-5, the binding energy for the tandem β-zipper interaction with Fn is distributed across the interface rather than concentrated in a small number of ″hot spot″ residues that are frequently observed in the interactions of folded proteins. We propose that this might be a common feature of the interactions of IDRs, and is likely to pose a challenge for the development of small molecule inhibitors of FnBP-mediated adhesion to and invasion of host cells.
|Subjects:||Q Science > Q Science (General)|
|Schools:||School of Applied Sciences|
School of Applied Sciences > Biomolecular Sciences Research Centre
|Depositing User:||Richard Bingham|
|Date Deposited:||13 Oct 2011 13:22|
|Last Modified:||17 Jan 2012 12:24|
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