Cryo-EM structure of RegIIIγ filaments reveals the molecular basis of its bactericidal activity.

Abstract

RegIII proteins execute their bactericidal activity by directly interacting with target cells and inducing cell death at acidic conditions. A previous report proposed that the antibacterial mechanism of RegIIIα is to form hexameric pores on the membrane of Gram-positive bacteria. Here, we investigated murine RegIIIγ, a homolog of RegIIIα. The cryo-EM structure of in vitro-assembled RegIIIγ filaments revealed conserved hexamer stacking and a distinct protofilament arrangement compared with RegIIIα filaments. Structure-guided mutagenesis studies showed that RegIIIγ functions as a monomer rather than a hexamer. Further experiments demonstrated that RegIIIγ catalyzes peptidoglycan degradation, yet this activity is not required for its bactericidal function. Additionally, we designed an assembly-deficient RegIIIγ mutant that exhibits bactericidal activity in both acidic and neutral conditions. Collectively, our findings provided a comprehensive understanding for RegIIIγ functions, offered novel insights into the bactericidal mechanism of RegIII proteins, and developed a promising candidate for the application of antimicrobial proteins.

Abstract as supplied by the indexing source. © the authors / publisher.