N-Glycans and sulfated glycosaminoglycans contribute to the action of diverse Tc toxins on mammalian cells.

ABSTRACT: Tc toxin is an exotoxin composed of three subunits named TcA, TcB and TcC. Structural analysis revealed that TcA can form homopentamer that mediates the cellular recognition and delivery processes, thus contributing to the host tropism of Tc toxin. N-glycans and heparan sulfates have been shown to act as receptors for several Tc toxins. Here, we performed two independent genome-wide CRISPR-Cas9 screens, and have validated glycans and sulfated glycosaminoglycans (sGAGs) as Tc toxin receptors also for previously uncharacterized Tc toxins. We found that TcdA1 form Photorhabdus luminescens W14 (TcdA1W14) can recognize N-glycans via the RBD-D domain, corroborating previous findings. Knockout of N-glycan processing enzymes specifically blocks the intoxication of TcdA1W14-assembled Tc toxin. On t

SUBMITTER: Song N 

PROVIDER: S-EPMC7861375 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature