Related Experiment Video
Updated: Sep 25, 2026

Kinetic Screening of Nuclease Activity using Nucleic Acid Probes
Published on: November 1, 2019
Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A
Isabella A Bennig1, Joel Ströbaek1, Rafael Mamede2,3
1Department of Clinical Sciences, Division of Infection Medicine, Lund University, Lund, Sweden.
Abstract:
Bacteria deploy virulence factors to subvert host immunity; yet the molecular details of these interactions often remain limited. Here, we reveal the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterize the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to SpnA. This allowed us to identify an additional oligonucleotide-binding domain, whose flexible structure may play an important function in nucleolytic activity. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex (MAC) C5b67 components as key interactors. Cross-linking mass spectrometry combined with integrative modeling identified the binding interfaces between SpnA and C5b67. These interfaces are conserved among genetically diverse S. pyogenes strains. Interaction between SpnA and C5b67 is suggested to prevent the assembly of a functional MAC. Our findings uncover a novel function of SpnA in complement inhibition, and identifies new potential targets to prevent and treat S. pyogenes infections.
Related Concept Videos
Determinants of Bacterial Pathogenicity and Virulence
Complement System
Streptococcal Pharyngitis
CRISPR and crRNAs
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
Antimicrobial Proteins
Interferons
Interferons (IFNs) are proteins produced by lymphocytes, macrophages, and fibroblasts infected with viruses. While IFNs cannot prevent viruses from entering and...
Gene Regulation in Microbial Communities: Quorum Sensing
