title: Structural insight into the role of Streptococcus parasanguinis Fap1 within oral biofilm formation.
abstract: The fimbriae-associated protein 1 (Fap1) is a major adhesin of Streptococcus parasanguinis, a primary colonizer of the oral cavity that plays an important role in the formation of dental plaque. Fap1 is an extracellular adhesive surface fibre belonging to the serine-rich repeat protein (SRRP) family, which plays a central role in the pathogenesis of streptococci and staphylococci. The N-terminal adhesive region of Fap1 (Fap1-NR) is composed of two domains (Fap1-NR(α) and Fap1-NR(β)) and is projected away from the bacterial surface via the extensive serine-rich repeat region, for adhesion to the salivary pellicle. The adhesive properties of Fap1 are modulated through a pH switch in which a reduction in pH results in a rearrangement between the Fap1-NR(α) and Fap1-NR(β) domains, which assists in the survival of S. parasanguinis in acidic environments. We have solved the structure of Fap1-NR(α) at pH 5.0 at 3.0Ǻ resolution and reveal how subtle rearrangements of the 3-helix bundle combined with a change in electrostatic potential mediates 'opening' and activation of the adhesive region. Further, we show that pH-dependent changes are critical for biofilm formation and present an atomic model for the inter-Fap1-NR interactions which have been assigned an important role in the biofilm formation.
authors.affiliation: Department of Biological Sciences, Centre for Structural Biology, Imperial College London, London, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Garnett
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Simpson
authors.forename: Jonathan
authors.initials: J
authors.lastname: Taylor
authors.forename: Stefi V
authors.initials: SV
authors.lastname: Benjamin
authors.forename: Camille
authors.initials: C
authors.lastname: Tagliaferri
authors.forename: Ernesto
authors.initials: E
authors.lastname: Cota
authors.forename: Yi-Ywan M
authors.initials: YY
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.forename: Stephen
authors.initials: S
authors.lastname: Matthews
mesh_terms: D018441:Biofilms; D018360:Crystallography, X-Ray; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D009055:Mouth / Q000382:microbiology*; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D055672:Static Electricity; D013291:Streptococcus / Q000502:physiology*
chemical_list: C403708:fap1 protein, Streptococcus; D036781:Fimbriae Proteins