title: Pneumococcal phosphoglycerate kinase interacts with plasminogen and its tissue activator.
abstract: Streptococcus pneumoniae is not only a commensal of the nasopharyngeal epithelium, but may also cause life-threatening diseases. Immune-electron microscopy studies revealed that the bacterial glycolytic enzyme, phosphoglycerate kinase (PGK), is localised on the pneumococcal surface of both capsulated and non-capsulated strains and colocalises with plasminogen. Since pneumococci may concentrate host plasminogen (PLG) together with its activators on the bacterial cell surface to facilitate the formation of plasmin, the involvement of PGK in this process was studied. Specific binding of human or murine PLG to strain-independent PGK was documented, and surface plasmon resonance analyses indicated a high affinity interaction with the kringle domains 1-4 of PLG. Crystal structure determination of pneumococcal PGK together with peptide array analysis revealed localisation of PLG-binding site in the N-terminal region and provided structural motifs for the interaction with PLG. Based on structural analysis data, a potential interaction of PGK with tissue plasminogen activator (tPA) was proposed and experimentally confirmed by binding studies, plasmin activity assays and thrombus degradation analyses.
authors.forename: M
authors.initials: M
authors.lastname: Fulde
authors.forename: N
authors.initials: N
authors.lastname: Bernardo-García
authors.forename: M
authors.initials: M
authors.lastname: Rohde
authors.forename: N
authors.initials: N
authors.lastname: Nachtigall
authors.forename: R
authors.initials: R
authors.lastname: Frank
authors.forename: K T
authors.initials: KT
authors.lastname: Preissner
authors.forename: J
authors.initials: J
authors.lastname: Klett
authors.forename: A
authors.initials: A
authors.lastname: Morreale
authors.forename: G S
authors.initials: GS
authors.lastname: Chhatwal
authors.forename: J A
authors.initials: JA
authors.lastname: Hermoso
authors.affiliation: Simone Bergmann, PhD, Technische Universität Braunschweig, Spielmannstrasse 7, 38106 Braunschweig, Germany, Tel.: +49 531 391 5818, Fax: +49 531 391 5854, E-mail: simone.bergmann@tu-bs.de.
authors.forename: S
authors.initials: S
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007820:Laryngeal Mucosa / Q000382:microbiology; D051379:Mice; D009297:Nasal Mucosa / Q000382:microbiology; D010735:Phosphoglycerate Kinase / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000235:genetics; D021381:Protein Transport; D013296:Streptococcus pneumoniae / Q000502:physiology*; D020349:Surface Plasmon Resonance; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010958:Plasminogen; D010735:Phosphoglycerate Kinase; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin
keywords: Angiostatin; Streptococcus pneumoniae; phosphoglycerate kinase; plasminogen; tissue-type plasminogen activator