Streptolysin O accelerates the conversion of plasminogen to plasmin
Abstract Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-11-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54173-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846147597458210816 |
|---|---|
| author | Di Tang Hamed Khakzad Elisabeth Hjortswang Lars Malmström Simon Ekström Lotta Happonen Johan Malmström |
| author_facet | Di Tang Hamed Khakzad Elisabeth Hjortswang Lars Malmström Simon Ekström Lotta Happonen Johan Malmström |
| author_sort | Di Tang |
| collection | DOAJ |
| description | Abstract Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the host-pathogen protein-protein interaction between plasminogen and streptolysin O, a key cytolytic toxin produced by GAS. This interaction accelerates the conversion of plasminogen to plasmin by both the host tissue-type plasminogen activator and streptokinase, a bacterial plasminogen activator secreted by GAS. Integrative structural mass spectrometry analysis shows that the interaction induces local conformational shifts in plasminogen. These changes lead to the formation of a stabilised intermediate plasminogen-streptolysin O complex that becomes significantly more susceptible to proteolytic processing by plasminogen activators. Our findings reveal a conserved and moonlighting pathomechanistic function for streptolysin O that extends beyond its well-characterised cytolytic activity. |
| format | Article |
| id | doaj-art-7a7df040b83f4bdcb65b329cdce788b1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7a7df040b83f4bdcb65b329cdce788b12024-12-01T12:35:33ZengNature PortfolioNature Communications2041-17232024-11-0115111510.1038/s41467-024-54173-6Streptolysin O accelerates the conversion of plasminogen to plasminDi Tang0Hamed Khakzad1Elisabeth Hjortswang2Lars Malmström3Simon Ekström4Lotta Happonen5Johan Malmström6Division of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityUniversité de Lorraine, CNRS, Inria, LORIADivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversitySciLifeLab, Integrated Structural Biology Platform, Structural Proteomics Unit Sweden, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityDivision of Infection Medicine, Department of Clinical Sciences Lund, Faculty of Medicine, Lund UniversityAbstract Group A Streptococcus (GAS) is a human-specific bacterial pathogen that can exploit the plasminogen-plasmin fibrinolysis system to dismantle blood clots and facilitate its spread and survival within the human host. In this study, we use affinity-enrichment mass spectrometry to decipher the host-pathogen protein-protein interaction between plasminogen and streptolysin O, a key cytolytic toxin produced by GAS. This interaction accelerates the conversion of plasminogen to plasmin by both the host tissue-type plasminogen activator and streptokinase, a bacterial plasminogen activator secreted by GAS. Integrative structural mass spectrometry analysis shows that the interaction induces local conformational shifts in plasminogen. These changes lead to the formation of a stabilised intermediate plasminogen-streptolysin O complex that becomes significantly more susceptible to proteolytic processing by plasminogen activators. Our findings reveal a conserved and moonlighting pathomechanistic function for streptolysin O that extends beyond its well-characterised cytolytic activity.https://doi.org/10.1038/s41467-024-54173-6 |
| spellingShingle | Di Tang Hamed Khakzad Elisabeth Hjortswang Lars Malmström Simon Ekström Lotta Happonen Johan Malmström Streptolysin O accelerates the conversion of plasminogen to plasmin Nature Communications |
| title | Streptolysin O accelerates the conversion of plasminogen to plasmin |
| title_full | Streptolysin O accelerates the conversion of plasminogen to plasmin |
| title_fullStr | Streptolysin O accelerates the conversion of plasminogen to plasmin |
| title_full_unstemmed | Streptolysin O accelerates the conversion of plasminogen to plasmin |
| title_short | Streptolysin O accelerates the conversion of plasminogen to plasmin |
| title_sort | streptolysin o accelerates the conversion of plasminogen to plasmin |
| url | https://doi.org/10.1038/s41467-024-54173-6 |
| work_keys_str_mv | AT ditang streptolysinoacceleratestheconversionofplasminogentoplasmin AT hamedkhakzad streptolysinoacceleratestheconversionofplasminogentoplasmin AT elisabethhjortswang streptolysinoacceleratestheconversionofplasminogentoplasmin AT larsmalmstrom streptolysinoacceleratestheconversionofplasminogentoplasmin AT simonekstrom streptolysinoacceleratestheconversionofplasminogentoplasmin AT lottahapponen streptolysinoacceleratestheconversionofplasminogentoplasmin AT johanmalmstrom streptolysinoacceleratestheconversionofplasminogentoplasmin |