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

IF 2.9 2区 材料科学 Q2 CHEMISTRY, MULTIDISCIPLINARY
IUCrJ Pub Date : 2024-05-01 DOI:10.1107/S2052252524001969
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.

昆虫耶尔森氏菌的 ABC 毒素复合物可以在展开状态下包装由不同基因位点表达的三种不同的细胞毒性成分:外壳和货物的结构。
细菌 ABC毒素复合物(Tcs)由三个核心蛋白组成:TcA、TcB 和 TcC。TcA 蛋白形成五聚体,附着在目标细胞表面并穿透细胞膜。TcB 和 TcC 蛋白组装成一个异源 TcB-TcC 亚复合物,形成一个空壳。这种 TcB-TcC 亚复合物会自我裂解,并在壳内封装由 TcC 蛋白 C 端区域编码的细胞毒性 "货物"。在这里,我们描述了一种以前未定性的 TcC 蛋白与 TcB 蛋白复合物的结构,TcC 蛋白由一个基因编码,其基因组位置与编码毒素复合物其他部分的基因相距甚远。当毒素被包裹在 TcB-TcC 外壳中时,C 端毒素呈现出一种未折叠的无序状态,有限的局部有序区域被类似于伴侣的外壳内表面所稳定。我们还测定了毒素货物单独的结构,结果表明,当毒素货物没有被外壳包裹时,它采用了与鼠伤寒沙门氏菌 SpvB 毒素催化结构域最相似的 ADP 核糖基转移酶折叠。我们的结构分析指出了一种可能的机制,即毒素直接作用于肌动蛋白,以一种阻止正常聚合的方式对其进行修饰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
IUCrJ
IUCrJ CHEMISTRY, MULTIDISCIPLINARYCRYSTALLOGRAPH-CRYSTALLOGRAPHY
CiteScore
7.50
自引率
5.10%
发文量
95
审稿时长
10 weeks
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.
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