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Title | An interbacterial NAD(P)(+) glycohydrolase toxin requires elongation factor Tu for delivery to target cells. |
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Journal, issue, pages | Cell, Vol. 163, Issue 3, Page 607-619, Year 2015 |
Publish date | Oct 22, 2015 |
Authors | 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 / |
PubMed Abstract | 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. |
External links | Cell / PubMed:26456113 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.401 - 21.5 Å |
Structure data | EMDB-3112: EMDB-3113: PDB-4zuy: PDB-4zv0: PDB-4zv4: |
Chemicals | ChemComp-CL: ChemComp-HOH: ChemComp-IOD: ChemComp-GDP: ChemComp-MG: |
Source |
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Keywords | PROTEIN BINDING / 4-helix bundle / bacterial type VI secretion immunity protein / Tse6 immunity protein / T6SS effector-immunity pair / TRANSLATION / T6SS effector / translation elongation factor |