Structural Basis for Regulation and Specificity of Fructooligosaccharide Import in Streptococcus pneumoniae

Abstract

Streptococcus pneumoniae is dependent on carbohydrate uptake for colonization and pathogenesis, and dedicates over a third of its transport systems to their uptake. The ability of the pneumococcus to utilize fructooligosaccharides (FOSs) is attributed to the presence of one of two types of FOS ATP-binding cassette (ABC) transporters. Strains encoding SfuABC are only able to utilize short-chain FOSs, while strains encoding FusABC can utilize both short- and long-chain FOSs. The crystal structures of the substrate-binding protein FusA in its open and closed conformations bound to FOSs, and solution scattering data of SfuA, delineate the structural basis for import of short- and long-chain FOSs. The structure of FusA identifies an EF hand-like calcium-binding motif. This is shown to be essential for translocation of FOSs in FusABC and forms the basis for the definition of a new class of substrate-binding proteins that regulate substrate translocation by calcium.