alpha-enolase, a novel strong plasmin(ogen) binding protein on the surface of pathogenic streptococci.
The plasmin(ogen) binding property of group A streptococci is incriminated in tissue invasion processes. We have characterized a novel 45-kDa protein displaying strong plasmin(ogen) binding activity from the streptococcal surface. Based on its biochemical properties, we confirmed the identity of this protein as alpha-enolase, a key glycolytic enzyme. Dose-dependent alpha-enolase activity, immune electron microscopy of whole streptococci using specific antibodies, and the opsonic nature of polyclonal and monoclonal antibodies concluded the presence of this protein on the streptococcal surface. We, henceforth, termed the 45-kDa protein, SEN (streptococcal surface enolase). SEN is found ubiquitously on the surface of most streptococcal groups and serotypes and showed significantly greater plasmin(ogen) binding affinity compared with previously reported streptococcal plasminogen binding proteins. Both the C-terminal lysine residue of SEN and a region N-terminal to it play a critical role in plasminogen binding. Results from competitive plasminogen binding inhibition assays and cross-linking studies with intact streptococci indicate that SEN contributes significantly to the overall streptococcal ability to bind plasmin(ogen). Our findings, showing both the protected protease activity of SEN-bound plasmin and SEN-specific immune responses, provide evidence for an important role of SEN in the disease process and post-streptococcal autoimmune diseases.
Pancholi
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Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York 10021, USA. panchov@rockvax.rockefeller.edu
Fischetti
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VA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry; D001667:Binding, Competitive; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000737:chemistry; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D010751:Phosphopyruvate Hydratase / Q000737:chemistry*; D010958:Plasminogen / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D012703:Serotyping; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000472:pathogenicity
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D008565:Membrane Proteins; D010958:Plasminogen; D005341:Fibrinolysin; C112984:streptococcal surface enolase; D010751:Phosphopyruvate Hydratase