Molecular basis of Fab-dependent IgA antibody recognition by gut-bacterial metallopeptidases

ABSTRACT: Immunoglobulin A (IgA) is essential for mucosal immunity and has been implicated in autoimmune diseases, such as IgA nephropathy. Certain pathogenic and commensal bacteria produce IgA proteases that selectively cleave IgA, potentially aiding bacterial colonization as well as suggesting therapeutic avenues for IgA nephropathy. Here, we investigate the substrate specificities of two IgA proteases of the M64 metallopeptidase family, ThomasA from Thomasclavelia ramosa and BF3526 from Bacteroides fragilis. Our structural, biochemical, and mutagenesis analyses demonstrate that ThomasA cleaves IgA through exclusive recognition of the Fab region. This mechanism is distinct from that of other antibody-specific peptidases, which typically require engagement of the Fc region. In contrast, X-ray cryst

SUBMITTER: Maria Angeles Marquez-Monino 

PROVIDER: S-SCDT-10_1038-S44318-025-00518-W | biostudies-other |

REPOSITORIES: biostudies-other