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

• Published in: IUCrJ Vol. 11; no. 3; pp. 299 - 308
• Main Authors: Busby, Jason N., Trevelyan, Sarah, Pegg, Cassandra L., Kerr, Edward D., Schulz, Benjamin L., Chassagnon, Irene, Landsberg, Michael J., Weston, Mitchell K., Hurst, Mark R. H., Lott, J. Shaun
• Format: Journal Article
• Language: English
• Published: England International Union of Crystallography 01.05.2024
• Subjects: abc toxins; Amino acids; ATP-Binding Cassette Transporters - chemistry; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Toxins - chemistry; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Cargo; Cell membranes; Crystallography, X-Ray; Cytotoxicity; Encapsulation; Genetic aspects; macromolecular machines; Models, Molecular; multi-protein complexes; Muscle proteins; protein structures; Proteins; Structural analysis; Toxins; Yersinia - genetics; yersinia entomophaga; Australia; protein structures; ABC toxins; macromolecular machines; Yersinia entomophaga; multi-protein complexes
• ISSN: 2052-2525; 2052-2525
• DOI: 10.1107/S2052252524001969

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.