National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI080609
米国
Defense Threat Reduction Agency (DTRA)
HDTRA-1-13-014
米国
引用
ジャーナル: Cell / 年: 2015 タイトル: An interbacterial NAD(P)(+) glycohydrolase toxin requires elongation factor Tu for delivery to target cells. 著者: John C Whitney / Dennis Quentin / Shin Sawai / Michele LeRoux / Brittany N Harding / Hannah E Ledvina / Bao Q Tran / Howard Robinson / Young Ah Goo / David R Goodlett / Stefan Raunser / Joseph D Mougous / 要旨: Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane ...Type VI secretion (T6S) influences the composition of microbial communities by catalyzing the delivery of toxins between adjacent bacterial cells. Here, we demonstrate that a T6S integral membrane toxin from Pseudomonas aeruginosa, Tse6, acts on target cells by degrading the universally essential dinucleotides NAD(+) and NADP(+). Structural analyses of Tse6 show that it resembles mono-ADP-ribosyltransferase proteins, such as diphtheria toxin, with the exception of a unique loop that both excludes proteinaceous ADP-ribose acceptors and contributes to hydrolysis. We find that entry of Tse6 into target cells requires its binding to an essential housekeeping protein, translation elongation factor Tu (EF-Tu). These proteins participate in a larger assembly that additionally directs toxin export and provides chaperone activity. Visualization of this complex by electron microscopy defines the architecture of a toxin-loaded T6S apparatus and provides mechanistic insight into intercellular membrane protein delivery between bacteria.