Work

Mechanism of trans-envelope bacterial polysaccharide secretion in Class-3 outer-membrane polysaccharide export (OPX) protein systems

Year: 2026

Type: article

Abstract: Bacterial secretion of extracellular polysaccharides is essential for surface colonization, biofilm formation, and pathogenesis. In diderm bacteria, such polymers traverse the periplasm and outer membrane (OM) through outer-membrane polysaccharide export (OPX) proteins that form secretion pores. Among them, Class-3 OPX proteins are the most widespread but lack an OM-spanning pore domain, leaving their mechanisms poorly understood. Here, we characterize WzaB from Myxococcus xanthus as a model for Class-3 OPX-mediated secretion. Structural and molecular dynamics analyses reveal that WzaB exists as a rigid monomer in solution, in contrast to the constitutive octamerization observed in Class-1 OPX proteins. Biochemical, biophysical, and in vivo analyses show that WzaB oligomerizes in a lipidation-dependent manner and directly interacts with the OM porin WzpB and the inner-membrane co-polymerase WzcB, with binding determinants mapped for both partners. Together, these proteins assemble into a trans-envelope polysaccharide secretion complex, redefining OPX function and revealing a distinct translocon architecture for Class-3 OPX systems. Bacteria secrete polysaccharides essential for colonization and infections. Here, the authors reveal the structure and mechanism of WzaB, a Class-3 OPX protein, uncovering a distinct trans-envelope secretion complex driving critical polysaccharide export in diderm bacteria.

Source: Nature Communications

DOI: 10.1038/s41467-025-67321-3