The ABC toxin complex from Yersinia entomophaga can package three different cytotoxic components expressed from distinct genetic loci in an unfolded state: the structures of both shell and cargo
Jason N. Busby , Sarah Trevelyan , Cassandra L. Pegg , Edward D. Kerr , Benjamin L. Schulz , Irene Chassagnon , Michael J. Landsberg , Mitchell K. Weston , Mark R. H. Hurst , J. Shaun Lott , A. Thorn (Editor)
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引用次数: 0
Abstract
A cytotoxin encoded by an ‘orphan’ genetic locus in the insect pathogen Yersinia entomophaga is shown to be a functional part of an ABC toxin complex, and the structures of both the RHS-repeat-containing ‘shell’ and the free toxin alone are determined by X-ray crystallography. The structure of the toxin indicates that it most likely functions by directly modifying actin in the target cell.
Bacterial ABC toxin complexes (Tcs) comprise three core proteins: TcA, TcB and TcC. The TcA protein forms a pentameric assembly that attaches to the surface of target cells and penetrates the cell membrane. The TcB and TcC proteins assemble as a heterodimeric TcB–TcC subcomplex that makes a hollow shell. This TcB–TcC subcomplex self-cleaves and encapsulates within the shell a cytotoxic ‘cargo’ encoded by the C-terminal region of the TcC protein. Here, we describe the structure of a previously uncharacterized TcC protein from Yersinia entomophaga, encoded by a gene at a distant genomic location from the genes encoding the rest of the toxin complex, in complex with the TcB protein. When encapsulated within the TcB–TcC shell, the C-terminal toxin adopts an unfolded and disordered state, with limited areas of local order stabilized by the chaperone-like inner surface of the shell. We also determined the structure of the toxin cargo alone and show that when not encapsulated within the shell, it adopts an ADP-ribosyltransferase fold most similar to the catalytic domain of the SpvB toxin from Salmonella typhimurium. Our structural analysis points to a likely mechanism whereby the toxin acts directly on actin, modifying it in a way that prevents normal polymerization.
期刊介绍:
IUCrJ is a new fully open-access peer-reviewed journal from the International Union of Crystallography (IUCr).
The journal will publish high-profile articles on all aspects of the sciences and technologies supported by the IUCr via its commissions, including emerging fields where structural results underpin the science reported in the article. Our aim is to make IUCrJ the natural home for high-quality structural science results. Chemists, biologists, physicists and material scientists will be actively encouraged to report their structural studies in IUCrJ.