A syringe-like injection mechanism inPhotorhabdus luminescenstoxins

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Abstract

Photorhabdus luminescensis an insect pathogenic bacterium that is symbiotic with entomopathogenic nematodes1. On invasion of insect larvae,P. luminescensis released from the nematodes and kills the insect through the action of a variety of virulence factors including large tripartite ABC-type toxin complexes2(Tcs). Tcs are typically composed of TcA, TcB and TcC proteins and are biologically active only when complete3,4,5. Functioning as ADP-ribosyltransferases, TcC proteins were identified as the actual functional components that induce actin-clustering, defects in phagocytosis and cell death5,6,7. However, little is known about the translocation of TcC into the cell by the TcA and TcB components. Here we show that TcA inP. luminescens(TcdA1) forms a transmembrane pore and report its structure in the prepore and pore state determined by cryoelectron microscopy. We find that the TcdA1 prepore assembles as a pentamer forming an α-helical, vuvuzela-shaped channel less than 1.5 nanometres in diameter surrounded by a large outer shell. Membrane insertion is triggered not only at low pH as expected, but also at high pH, explaining Tc action directly through the midgut of insects8. Comparisons with structures of the TcdA1 pore inserted into a membrane and in complex with TcdB2 and TccC3 reveal large conformational changes during membrane insertion, suggesting a novel syringe-like mechanism of protein translocation. Our results demonstrate how ABC-type toxin complexes bridge a membrane to insert their lethal components into the cytoplasm of the host cell. We believe that the proposed mechanism is characteristic of the whole ABC-type toxin family. This explanation of toxin translocation is a step towards understanding the host–pathogen interaction and the complex life cycle ofP. luminescensand other pathogens, including human pathogenic bacteria, and serves as a strong foundation for the development of biopesticides.

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