title: 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.
authors.affiliation: Diamond House, Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot OX11 0FA, UK.
authors.forename: Simone
authors.initials: S
authors.lastname: Culurgioni
authors.affiliation: Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot OX11 0FA, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Harris
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA.
authors.forename: Anirudh K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: King
authors.affiliation: Diamond House, Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK; Research Complex at Harwell, Harwell Science and Innovation Campus, Didcot OX11 0FA, UK. Electronic address: martin.walsh@diamond.ac.uk.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walsh
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray; D020832:EF Hand Motifs; D053263:Gene Regulatory Networks; D008958:Models, Molecular; D009844:Oligosaccharides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D009844:Oligosaccharides; C116580:fructooligosaccharide; D002118:Calcium
keywords: Streptococcus pneumoniae; calcium signaling; carbohydrate ABC transporters; substrate translocation regulation; substrate-binding proteins