Architectural asymmetry enables DNA transport through theHelicobacter pylori cagtype IV secretion system

Abstract

ABSTRACTStructural asymmetry within secretion system architecture is fundamentally important for apparatus diversification and biological function. However, the mechanism by which symmetry mismatch contributes to nanomachine assembly and interkingdom effector translocation are undefined. Here, we show that architectural asymmetry orchestrates dynamic substrate selection and enables trans-kingdom DNA conjugation through theHelicobacter pylori cagtype IV secretion system (cagT4SS). Structural analyses of asymmetric units within thecagT4SS periplasmic ring complex (PRC) revealed intermolecular π-π stacking interactions that coordinate DNA binding and license trans-kingdom conjugation without disrupting the translocation of protein and peptidoglycan effector molecules. Additionally, we identified a novel proximal translocation channel gating mechanism that regulates cargo loading and governs substrate transport across the outer membrane. We thus propose a model whereby the organization and geometry of architectural symmetry mismatch exposes π−π interfaces within the PRC to facilitate DNA transit through thecagT4SS translocation channel.