Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their β‐domains. Issue 9 (7th March 2013)

• Record Type: Journal Article
• Authors: Zhang, Yueling; Liang, Zhong; Glinton, Kristofor; Ploplis, Victoria A.; Castellino, Francis J.
• Is Part Of: FEBS letters. Volume 587:Issue 9(2013)
• Page Start: 1304
• Page End: 1309
• Publication Date: 2013-03-07
• Subjects: Streptokinase -- Fibrinolysis -- Protein domains -- Virulence -- Streptococcus pyogenes; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.02.033
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Cluster 1 streptokinases (SK1) from Streptococcus pyogenes (GAS) show substantially higher human plasminogen (hPg) activation activities and tighter hPg binding affinities than cluster 2b streptokinases (SK2b) in solution. The extent to which the different domains of SK are responsible for these differences is unknown. We exchanged each of the three known SK domains (α, β, and γ) between SK1 and SK2b and assessed the function of the resulting variants. Our results show that primary structural differences in the β‐domains dictate these functional differences. This first report on the primary structure–functional relationship between naturally occurring SK1 and SK2b sheds new light on the mechanism of hPg activation by SK, a critical virulence determinant in this species of human pathogenic bacteria. Abstract : ► Two types of streptokinases (SK) have been found in different Streptococcus pyogenes strains, SK1 and SK2b. ► SK2b activity requires cell surface plasminogen receptors and SK1 does not. ► SK2b activity can be converted into SK1 activity by exchange of their β‐domains.