title: Fructose-1,6-bisphosphate aldolase of Neisseria meningitidis binds human plasminogen via its C-terminal lysine residue.
abstract: Neisseria meningitidis is a leading cause of fatal sepsis and meningitis worldwide. As for commensal species of human neisseriae, N. meningitidis inhabits the human nasopharynx and asymptomatic colonization is ubiquitous. Only rarely does the organism invade and survive in the bloodstream leading to disease. Moonlighting proteins perform two or more autonomous, often dissimilar, functions using a single polypeptide chain. They have been increasingly reported on the surface of both prokaryotic and eukaryotic organisms and shown to interact with a variety of host ligands. In some organisms moonlighting proteins perform virulence-related functions, and they may play a role in the pathogenesis of N. meningitidis. Fructose-1,6-bisphosphate aldolase (FBA) was previously shown to be surface-exposed in meningococci and involved in adhesion to host cells. In this study, FBA was shown to be present on the surface of both pathogenic and commensal neisseriae, and surface localization and anchoring was demonstrated to be independent of aldolase activity. Importantly, meningococcal FBA was found to bind to human glu-plasminogen in a dose-dependent manner. Site-directed mutagenesis demonstrated that the C-terminal lysine residue of FBA was required for this interaction, whereas subterminal lysine residues were not involved.
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Fariza
authors.initials: F
authors.lastname: Shams
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Oldfield
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Si Kei
authors.initials: SK
authors.lastname: Lai
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Sarfraz A
authors.initials: SA
authors.lastname: Tunio
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Wooldridge
authors.affiliation: School of Life Sciences, Molecular Bacteriology and Immunology Group, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
authors.forename: David P J
authors.initials: DP
authors.lastname: Turner
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008239:Lysine; D009154:Mutation; D009345:Neisseria meningitidis / Q000201:enzymology* / Q000235:genetics; D010958:Plasminogen / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D010958:Plasminogen; D005634:Fructose-Bisphosphate Aldolase; D008239:Lysine
keywords: Aldolase; Neisseria meningitidis; pathogenesis; plasminogen; protein moonlighting.