title: The choline-binding protein PspC of Streptococcus pneumoniae interacts with the C-terminal heparin-binding domain of vitronectin.
abstract: Adherence of Streptococcus pneumoniae is directly mediated by interactions of adhesins with eukaryotic cellular receptors or indirectly by exploiting matrix and serum proteins as molecular bridges. Pneumococci engage vitronectin, the human adhesive glycoprotein and complement inhibitor, to facilitate attachment to epithelial cells of the mucosal cavity, thereby modulating host cell signaling. In this study, we identified PspC as a vitronectin-binding protein interacting with the C-terminal heparin-binding domain of vitronectin. PspC is a multifunctional surface-exposed choline-binding protein displaying various adhesive properties. Vitronectin binding required the R domains in the mature PspC protein, which are also essential for the interaction with the ectodomain of the polymeric immunoglobulin receptor and secretory IgA. Consequently, secretory IgA competitively inhibited binding of vitronectin to purified PspC and to PspC-expressing pneumococci. In contrast, Factor H, which binds to the N-terminal part of mature PspC molecules, did not interfere with the PspC-vitronectin interaction. Using a series of vitronectin peptides, the C-terminal heparin-binding domain was shown to be essential for the interaction of soluble vitronectin with PspC. Binding experiments with immobilized vitronectin suggested a region N-terminal to the identified heparin-binding domain as an additional binding region for PspC, suggesting that soluble, immobilized, as well as cellularly bound vitronectin possesses different conformations. Finally, vitronectin bound to PspC was functionally active and inhibited the deposition of the terminal complement complex. In conclusion, this study identifies and characterizes (on the molecular level) the interaction between the pneumococcal adhesin PspC and the human glycoprotein vitronectin.
authors.affiliation: Department of Genetics of Microorganisms, Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Voss
authors.forename: Teresia
authors.initials: T
authors.lastname: Hallström
authors.forename: Malek
authors.initials: M
authors.lastname: Saleh
authors.forename: Gerhard
authors.initials: G
authors.lastname: Burchhardt
authors.forename: Thomas
authors.initials: T
authors.lastname: Pribyl
authors.forename: Birendra
authors.initials: B
authors.lastname: Singh
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013296:Streptococcus pneumoniae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019096:Vitronectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C110344:SpsA protein, Streptococcus pneumoniae; D019096:Vitronectin
keywords: Adhesin; Bacterial Pathogenesis; Complement; Extracellular Matrix; Pneumococci; Protein-Protein Interactions; PspC; Surface Plasmon Resonance (SPR); Virulence Factors