Inositol Hexakisphosphate-Induced Autoprocessing of Large Bacterial Protein Toxins

PLoS Pathogens

Karla J. F. Satchell¹  Martina Egerer¹ 

[1] Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America

关键词: Toxins;    Cytosol;    Crystal structure;    Clostridium difficile;    Eukaryota;    Proteases;    Protein structure;    Bacterial pathogens;   

DOI  :  10.1371/journal.ppat.1000942

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Large bacterial protein toxins autotranslocate functional effector domains to the eukaryotic cell cytosol, resulting in alterations to cellular functions that ultimately benefit the infecting pathogen. Among these toxins, the clostridial glucosylating toxins (CGTs) produced by Gram-positive bacteria and the multifunctional-autoprocessing RTX (MARTX) toxins of Gram-negative bacteria have distinct mechanisms for effector translocation, but a shared mechanism of post-translocation autoprocessing that releases these functional domains from the large holotoxins. These toxins carry an embedded cysteine protease domain (CPD) that is activated for autoprocessing by binding inositol hexakisphosphate (InsP6), a molecule found exclusively in eukaryotic cells. Thus, InsP6-induced autoprocessing represents a unique mechanism for toxin effector delivery specifically within the target cell. This review summarizes recent studies of the structural and molecular events for activation of autoprocessing for both CGT and MARTX toxins, demonstrating both similar and potentially distinct aspects of autoprocessing among the toxins that utilize this method of activation and effector delivery.

【 授权许可】

CC BY