The β-domain of cluster 2b streptokinase is a major determinant for the regulation of its plasminogen activation activity by cellular plasminogen receptors.
Cluster 2b streptokinase (SK2b), secreted by invasive skin-trophic strains of Streptococcus pyogenes (GAS), is a human plasminogen (hPg) activator that optimally functions when human plasma hPg is bound, via its kringle-2 domain, to cognizant bacterial cells through the a1a2 domain of the major cellular hPg receptor, Plasminogen-binding group A streptococcal M-like protein (PAM). Another class of streptokinases (SK1), secreted primarily by GAS strains that possess affinity for pharyngeal infections, does not require PAM-bound hPg for optimal activity. We find herein that replacement of the central β-domain of SK2b with the same module from SK1 reduces the dependency of SK2b on PAM, and the converse is true when the β-domain of SK1 is replaced with this same region of SK2b. These data suggest that simple evolutionary shuttling of protein domains in GAS can be employed by GAS to rapidly generate strains that differ in tissue tropism and invasive capability and allow the bacteria to survive different challenges by the host.
W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; Institute of Animal Sciences, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China.
Yueling
Y
Zhang
W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Jeffrey A
JA
Mayfield
W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.
Victoria A
VA
Ploplis
W.M. Keck Center for Transgene Research and Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. Electronic address: fcastell@nd.edu.
Francis J
FJ
Castellino
D054884:Host-Pathogen Interactions; D006801:Humans; D018082:Kringles; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D010960:Plasminogen Activators / Q000737:chemistry / Q000378:metabolism*; D013290:Streptococcal Infections / Q000201:enzymology / Q000821:virology*; D013297:Streptococcus pyogenes / Q000737:chemistry / Q000201:enzymology* / Q000472:pathogenicity / Q000502:physiology*; D013300:Streptokinase / Q000737:chemistry / Q000378:metabolism*
D010958:Plasminogen; D013300:Streptokinase; D010960:Plasminogen Activators
Bacterial virulence; Human plasminogen; Protein domains; Streptococcus pyogenes; Streptokinase