Dataset Information

Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their ?-domains.

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 (?, ?, and ?) between SK1 and SK2b and assessed the function of the resulting variants. Our results show that primary structural differences in the ?-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.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC3740169 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their β-domains.

Zhang Yueling Y Liang Zhong Z Glinton Kristofor K Ploplis Victoria A VA Castellino Francis J FJ

FEBS letters 20130307 9

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 di ...[more]

PMID: 23474243

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Project description:The ExPortal of Streptococcus pyogenes is a focal microdomain of the cytoplasmic membrane that clusters the translocons of the general secretory pathway with accessory factors to facilitate the maturation of secreted polypeptides. While it is known that the ExPortal is enriched in anionic lipids, the mechanisms that organize the ExPortal are poorly understood. In the present study, we examined the role of the cell wall in organizing and maintaining the ExPortal. Removal of the cell wall resulted in a loss of ExPortal focal integrity accompanied by the circumferential redistribution of ExPortal lipid and protein components. A similar loss occurred upon treatment with gallidermin, a nonpermeabilizing lantibiotic that targets the lipid II precursor of peptidoglycan synthesis, and this treatment disrupted the secretion of several ExPortal substrates. Furthermore, several enzymes involved in the membrane-associated steps of lipid II synthesis, including MraY and MurN, were found to localize to a single discrete focus in the membrane that was coincident with the focal location of the secretory translocons and the anionic lipid microdomain. These data suggest that the ExPortal is associated with the site of peptidoglycan precursor synthesis and that peptidoglycan biogenesis influences ExPortal organization. These data add to an emerging literature indicating that cell wall biogenesis, cell division, and protein secretion are spatially coorganized processes.Since Gram-positive bacteria lack a periplasmic space, they lack a protected compartment to spatially coordinate interaction between newly secreted proteins and the factors required to process them. This represents a significant problem for pathogens that depend on the secretion of toxins and cell wall-associated adhesins to cause disease. Streptococci solve this dilemma by restricting secretion and processing factors to a defined region of the membrane. However, the mechanisms that promote restriction are not understood. In this study, we show that restriction of these factors in the pathogen Streptococcus pyogenes is intimately linked with the presence of the cell wall and its synthesis. Furthermore, several cell wall synthesis proteins are also restricted to the site of protein secretion. This study contributes to our understanding of how the Gram-positive cell is organized to coordinate protein secretion and biogenesis with cell wall synthesis and to the ongoing development of antibiotics that target these processes.

Dataset Information

Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their ?-domains.

Publications

Functional differences between Streptococcus pyogenes cluster 1 and cluster 2b streptokinases are determined by their β-domains.

Similar Datasets

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