Streptococcus pyogenes nuclease A interferes with host complement functions
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| Titel: | Streptococcus pyogenes nuclease A interferes with host complement functions |
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| Autoren: | A. Bennig, Isabella, Ströbaek, Joel, Mamede, Rafael, Neumann, Ariane, Friães, Ana, Ramirez, Mario, Hall, Michael, Collin, Mattias, Malmström, Lars, Ekström, Simon, Frick, Inga-Maria, Björck, Lars, Happonen, Lotta J. |
| Weitere Verfasser: | Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Infect@LU, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Infect@LU, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Infection Medicine (BMC), Structural Infection Medicine (STRIME), Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Infektionsmedicin, Strukturell infektionsmedicin, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Infection Medicine (BMC), epIgG, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Infektionsmedicin, epIgG, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Infection Medicine (BMC), Translational infection medicine, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Infektionsmedicin, Translationell infektionsmedicin, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Infection Medicine (BMC), Infection and immunomodulation, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Infektionsmedicin, Infektion och immunmodulering, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section V, Mass Spectrometry, BioMS, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion V, Masspektrometri, BioMS, Originator, Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Section III, Infection Medicine (BMC), Molecular Pathogenesis, Lunds universitet, Medicinska fakulteten, Institutionen för kliniska vetenskaper, Lund, Sektion III, Infektionsmedicin, Molekylär patogenes, Originator |
| Quelle: | :1-16 |
| Schlagwörter: | Natural Sciences, Biological Sciences, Structural Biology, Naturvetenskap, Biologi, Strukturbiologi |
| Beschreibung: | Bacterial pathogens deploy diverse virulence factors to subvert host immunity, yet the molecular details of these interactions often remain unresolved. Here, we investigate the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterized the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to this protein. This allowed us to identify an additional oligonucleotide-binding domain whose flexible structure may play an important function in the nucleolytic activity of SpnA. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex C5b67 components as key interactors in human plasma. Cross-linking mass spectrometry combined with integrative modeling identified the direct binding interfaces between SpnA and C5b67. These interfaces are highly conserved among genetically diverse S. pyogenes strains. The interaction between SpnA andC5b67 is suggested to prevent the assembly of a functional membrane attack complex. Taken together, our findings uncover a novel function of SpnA in complement inhibition and identifies new potential targets to prevent and treat S. pyogenes infections. |
| Zugangs-URL: | https://doi.org/10.1101/2025.08.25.672074 |
| Datenbank: | SwePub |
Nájsť tento článok vo Web of Science | Abstract: | Bacterial pathogens deploy diverse virulence factors to subvert host immunity, yet the molecular details of these interactions often remain unresolved. Here, we investigate the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterized the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to this protein. This allowed us to identify an additional oligonucleotide-binding domain whose flexible structure may play an important function in the nucleolytic activity of SpnA. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex C5b67 components as key interactors in human plasma. Cross-linking mass spectrometry combined with integrative modeling identified the direct binding interfaces between SpnA and C5b67. These interfaces are highly conserved among genetically diverse S. pyogenes strains. The interaction between SpnA andC5b67 is suggested to prevent the assembly of a functional membrane attack complex. Taken together, our findings uncover a novel function of SpnA in complement inhibition and identifies new potential targets to prevent and treat S. pyogenes infections. |
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| DOI: | 10.1101/2025.08.25.672074 |