title: Molecular Interactions of Human Plasminogen with Fibronectin-binding Protein B (FnBPB), a Fibrinogen/Fibronectin-binding Protein from Staphylococcus aureus.
abstract: Staphylococcus aureus is a commensal bacterium that has the ability to cause superficial and deep-seated infections. Like several other invasive pathogens, S. aureus can capture plasminogen from the human host where it can be converted to plasmin by host plasminogen activators or by endogenously expressed staphylokinase. This study demonstrates that sortase-anchored cell wall-associated proteins are responsible for capturing the bulk of bound plasminogen. Two cell wall-associated proteins, the fibrinogen- and fibronectin-binding proteins A and B, were found to bind plasminogen, and one of them, FnBPB, was studied in detail. Plasminogen captured on the surface of S. aureus- or Lactococcus lactis-expressing FnBPB could be activated to the potent serine protease plasmin by staphylokinase and tissue plasminogen activator. Plasminogen bound to recombinant FnBPB with a KD of 0.532 μm as determined by surface plasmon resonance. Plasminogen binding did not to occur by the same mechanism through which FnBPB binds to fibrinogen. Indeed, FnBPB could bind both ligands simultaneously indicating that their binding sites do not overlap. The N3 subdomain of FnBPB contains the full plasminogen-binding site, and this includes, at least in part, two conserved patches of surface-located lysine residues that were recognized by kringle 4 of the host protein.
authors.affiliation: From the Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy and.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Pietrocola
authors.affiliation: From the Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy and.
authors.forename: Giulia
authors.initials: G
authors.lastname: Nobile
authors.affiliation: From the Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy and.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gianotti
authors.affiliation: the Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, University of Dublin, Dublin 2, Ireland.
authors.forename: Marta
authors.initials: M
authors.lastname: Zapotoczna
authors.affiliation: the Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, University of Dublin, Dublin 2, Ireland.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Foster
authors.affiliation: the Department of Microbiology, Moyne Institute of Preventive Medicine, School of Genetics and Microbiology, Trinity College, University of Dublin, Dublin 2, Ireland geoghegj@tcd.ie.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.affiliation: From the Department of Molecular Medicine, Unit of Biochemistry, University of Pavia, 27100 Pavia, Italy and pspeziale@unipv.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Speziale
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C078635:fibronectin-binding proteins, bacterial; D010958:Plasminogen
keywords: Staphylococcus aureus (S. aureus); bacterial pathogenesis; cell surface protein; fibrinogen; plasminogen; tissue plasminogen activator (tPA)