AE-MS to profile SLO-human plasma protein interactome landscape; HDX-MS and XL-MS to study protein interaction and dynamics of PLG-SLO

Group A Streptococcus is known to exploit the human fibrinolysis system, particularly by targeting the plasminogen/plasmin pathway through redundant pathomechanisms. In this study, we began with affinity-enrichment mass spectrometry to map the interaction landscape between streptolysin O and human plasma, identifying human plasminogen as a specific binder to the streptolysin O. Subsequent biochemical assays validated this direct interaction and demonstrated the streptolysin O's role in enhancing tPA-mediated plasmin production. We then employed HDX-MS and XL-MS to further explore and characterize the molecular details of the plasminogen-streptolysin O complex formation, shedding light on its biological significance.