Stein P E, Boodhoo A, Tyrrell G J, Brunton J L, Read R J
Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Canada.
Nature. 1992 Feb 20;355(6362):748-50. doi: 10.1038/355748a0.
The Shiga toxin family, a group of cytotoxins associated with diarrhoeal diseases and the haemolytic uraemic syndrome, includes Shiga toxin from Shigella dysenteriae type 1 and verotoxins produced by enteropathogenic Escherichia coli. The family belongs to the A-B class of bacterial toxins, which includes the cholera toxin family, pertussis and diphtheria toxins. These toxins all have bipartite structures consisting of an enzymatic A subunit associated with a B oligomer which binds to specific cell-surface receptors, but their amino-acid sequences and pathogenic mechanisms differ. We have determined the crystal structure of the B oligomer of verotoxin-1 from E. coli. The structure unexpectedly resembles that of the B oligomer of the cholera toxin-like heat-labile enterotoxin from E. coli, despite the absence of detectable sequence similarity between these two proteins. This result implies a distant evolutionary relationship between the Shiga toxin and cholera toxin families. We suggest that the cell surface receptor-binding site lies in a cleft between adjacent subunits of the B pentamer, providing a potential target for drugs and vaccines to prevent toxin binding and effect.
志贺毒素家族是一组与腹泻疾病和溶血尿毒综合征相关的细胞毒素，包括痢疾志贺氏菌1型产生的志贺毒素和肠致病性大肠杆菌产生的维罗毒素。该家族属于细菌毒素的A-B类，其中包括霍乱毒素家族、百日咳毒素和白喉毒素。这些毒素均具有二分结构，由与B寡聚体相关的酶促A亚基组成，B寡聚体与特定的细胞表面受体结合，但它们的氨基酸序列和致病机制有所不同。我们已经确定了大肠杆菌维罗毒素-1的B寡聚体的晶体结构。尽管这两种蛋白质之间没有可检测到的序列相似性，但该结构意外地类似于大肠杆菌霍乱毒素样热不稳定肠毒素的B寡聚体结构。这一结果暗示了志贺毒素家族与霍乱毒素家族之间存在遥远的进化关系。我们认为细胞表面受体结合位点位于B五聚体相邻亚基之间的裂隙中，这为预防毒素结合和作用的药物及疫苗提供了潜在靶点。
