Abstract
Clostridioides difficileis a Gram-positive, pathogenic bacterium and a prominent cause of hospital-acquired diarrhea in the United States. The symptoms ofC. difficileinfection are caused by the activity of three large toxins known as toxin A (TcdA), toxin B (TcdB), and theC. difficiletransferase toxin (CDT). Reported here is a 3.8-Å cryo–electron microscopy (cryo-EM) structure of CDT, a bipartite toxin comprised of the proteins CDTa and CDTb. We observe a single molecule of CDTa bound to a CDTb heptamer. The formation of the CDT complex relies on the interaction of an N-terminal adaptor and pseudoenzyme domain of CDTa with six subunits of the CDTb heptamer. CDTb is observed in a preinsertion state, a conformation observed in the transition of prepore to β-barrel pore, although we also observe a single bound CDTa in the prepore and β-barrel conformations of CDTb. The binding interaction appears to prime CDTa for translocation as the adaptor subdomain enters the lumen of the preinsertion state channel. These structural observations advance the understanding of how a single protein, CDTb, can mediate the delivery of a large enzyme, CDTa, into the cytosol of mammalian cells.
Funder
U.S. Department of Veterans Affairs
HHS | NIH | National Institute of Allergy and Infectious Diseases
HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases
HHS | NIH | National Institute of General Medical Sciences
Publisher
Proceedings of the National Academy of Sciences
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献