title: Identification and structural basis of binding to host lung glycogen by streptococcal virulence factors.
abstract: The ability of pathogenic bacteria to recognize host glycans is often essential to their virulence. Here we report structure-function studies of previously uncharacterized glycogen-binding modules in the surface-anchored pullulanases from Streptococcus pneumoniae (SpuA) and Streptococcus pyogenes (PulA). Multivalent binding to glycogen leads to a strong interaction with alveolar type II cells in mouse lung tissue. X-ray crystal structures of the binding modules reveal a novel fusion of tandem modules into single, bivalent functional domains. In addition to indicating a structural basis for multivalent attachment, the structure of the SpuA modules in complex with carbohydrate provides insight into the molecular basis for glycogen specificity. This report provides the first evidence that intracellular lung glycogen may be a novel target of pathogenic streptococci and thus provides a rationale for the identification of the streptococcal alpha-glucan-metabolizing machinery as virulence factors.
authors.affiliation: Biochemistry & Microbiology, University of Victoria, PO Box 3055 STN CSC, Victoria, British Columbia, V8W 3P6, Canada.
authors.forename: Alicia Lammerts
authors.initials: AL
authors.lastname: van Bueren
authors.forename: Melanie
authors.initials: M
authors.lastname: Higgins
authors.forename: Diana
authors.initials: D
authors.lastname: Wang
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burke
authors.forename: Alisdair B
authors.initials: AB
authors.lastname: Boraston
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D005936:Glucans / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000201:enzymology / Q000378:metabolism / Q000472:pathogenicity*; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D005936:Glucans; D008024:Ligands; D037521:Virulence Factors; D006003:Glycogen; D006026:Glycoside Hydrolases; C100181:pullulanase