Related Experiment Video
Updated: May 5, 2026

Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Site-restricted plasminogen activation mediated by group A streptococcal streptokinase variants
Simon M Cook1, Amanda Skora1, Mark J Walker2
1*Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Wollongong, NSW, Australia.
Abstract:
SK (streptokinase) is a secreted plasminogen activator and virulence factor of GAS (group A Streptococcus). Among GAS isolates, SK gene sequences are polymorphic and are grouped into two sequence clusters (cluster type-1 and cluster type-2) with cluster type-2 being further classified into subclusters (type-2a and type-2b). In the present study, we examined the role of bacterial and host-derived cofactors in SK-mediated plasminogen activation. All SK variants, apart from type-2b, can form an activator complex with Glu-Plg (Glu-plasminogen). Specific ligand-binding-induced conformational changes in Glu-Plg mediated by fibrinogen, PAM (plasminogen-binding group A streptococcal M protein), fibrinogen fragment D or fibrin, were required for type-2b SK to form a functional activator complex with Glu-Plg. In contrast with type-1 and type-2a SK, type-2b SK activator complexes were inhibited by α2-antiplasmin unless bound to fibrin or to the GAS cell-surface via PAM in combination with fibrinogen. Taken together, these data suggest that type-2b SK plasminogen activation may be restricted to specific microenvironments within the host such as fibrin deposits or the bacterial cell surface through the action of α2-antiplasmin. We conclude that phenotypic SK variation functionally underpins a pathogenic mechanism whereby SK variants differentially focus plasminogen activation, leading to specific niche adaption within the host.
Related Concept Videos
Staphylococcal Skin Infections
Formation of the Platelet Plug
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
Clot Retraction and Fibrinolysis
Introduction to Hemostasis
The three phases of hemostasis involve many clotting factors present in plasma and several substances released by platelets and injured tissue cells. It is a fast, localized,...
Cytoskeletal Linker Proteins - Plakins
Conservative Site-specific Recombination and Phase Variation
The recognition sites for Cre recombinase called LoxP...

