Bivalent Ligation of the Collagen-binding Modules of Fibronectin by SFS, a Non-anchored Bacterial Protein of Streptococcus equi

Abstract

Background: Streptococcus equi expresses SFS protein that contains a disordered region, R1R2, able to inhibit the collagenfibronectin interaction. Results: The repeats of R1R2 bind to plasma fibronectin via modules 8-9 FNI in a two-step reaction involving both fibronectin subunits. Conclusion:8-9 FNI modules of compact fibronectin are arranged in a way that captures R1R2 efficiently. Significance: The same strategy may be used to engage collagen.

Dynamic structure of plasma fibronectin

“…The physiological relevance of the structure in Zn 2+ is unclear; for instance, the concentrations of Zn 2+ required for crystallization do not support binding of a collagenous peptide to the gelatin-binding domain (Graille et al, 2010). Further, binding to 8-9 FNI of polypeptides derived from bacterial surface proteins was abolished in the presence of Zn 2+ (Maurer et al, 2010, Ma et al, 2015a). However, the radically different structures of 8 FNI within the whole gelatin-binding domain in Zn 2+ compared to the tandem 8-9 FNI construct indicate that this region in FN has the potential to undergo major conformational rearrangements.…”

“…R1R2 contains two identical short GxxGE collagen-like repeats and binds to plasma fibronectin via modules 8-9 FNI in a two-step reaction involving both fibronectin subunits (Ma et al, 2015a). Fig.…”

“…At this temperature, there is partial unfolding of collagen at the “3/4 site” in proximity to the GxxGE motif where there is no proline over a stretch of 6 Gxx triplets (Stultz, 2002, Leikina et al, 2002, An et al, 2014). FN may mimic binding to the two repeats of R1R2 by associating with locally denatured sequences of two of the three subunits of type I collagen in a high affinity interaction (Ma et al, 2015a). A key consequence of this model is that for assembled FN to bind to, and possibly facilitate assembly of, nascent type I collagen, the two 8 FNI modules must remain in proximity after incorporation of FN into extracellular matrix (Fig.…”

Base molecular dos fatores de virulência de Streptococcus equi

“…O gene fne apresenta uma deleção em uma base na metade do gene expressando-se somente um segmento do mesmo pela formação de um códon de parada na fase de leitura aberta (Harrington et al, 2000), esta deleção é conservada em todos os isolados S. equi analisados, resultando na perda da âncora de superfície LPXTG e leva à produção de um produto secretado, o FNE, que liga-se a fibronectina e colágeno o que provoca um incremento na virulência de S. equi (Lindmark et al, 2001;Holden et al, 2009). O gene sfs codifica a proteína de 40kda SFS que difere da sequência de aminoácidos de FNE (Lindmark e Guss, 1999), SFS é uma proteína de ligação da fibronectina de cepas patogénicas de S. equi, e pode inibir a ligação da fibronectina com o colágeno, uma vez que as ligações de SFS e do colágeno são similares (Lindmark e Guss, 1999;Ma et al, 2015).…”

Targeting Fibronectin To Disrupt In Vivo Candida albicans Biofilms

“…For maturation assays, C. albicans was incubated for 1 h (37°C), nonadherent cells were removed, and host proteins in RPMI medium-MOPS were added for 18 h prior to the XTT assay. For the blocking experiments, FUD was included at 500 nM (11,12). This peptide sequence is based on a Streptococcus pyogenes adhesin domain, which competitively binds the fibronectin type 1 module, inhibiting fibrillogenesis (11,12).…”