Dataset Information

Structural and functional analysis of the tandem ?-zipper interaction of a Streptococcal protein with human fibronectin.

ABSTRACT: 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 ?-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 ?-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.

SUBMITTER: Norris NC

PROVIDER: S-EPMC3207447 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Structural and functional analysis of the tandem β-zipper interaction of a Streptococcal protein with human fibronectin.

Norris Nicole C NC Bingham Richard J RJ Harris Gemma G Speakman Adrian A Jones Richard P O RPO Leech Andrew A Turkenburg Johan P JP Potts Jennifer R JR

The Journal of biological chemistry 20110812 44

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 interactio ...[more]

PMID: 21840989

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Dataset Information

Structural and functional analysis of the tandem ?-zipper interaction of a Streptococcal protein with human fibronectin.

Publications

Structural and functional analysis of the tandem β-zipper interaction of a Streptococcal protein with human fibronectin.

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