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

Nicole C. Norris, Richard J. Bingham, Gemma Harris, Adrian Speakman, Richard P O Jones, Andrew P. Leech, Johan P. Turkenburg, Jennifer R. Potts

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)38311-38320
Number of pages10
JournalJournal of Biological Chemistry
Issue number44
Publication statusPublished - 4 Nov 2011


Dive into the research topics of 'Structural and functional analysis of the tandem β-zipper interaction of a streptococcal protein with human fibronectin'. Together they form a unique fingerprint.

Cite this