Blood group antigen recognition by Escherichia coli heat-labile enterotoxin
Blood group antigen recognition by Escherichia coli heat-labile enterotoxin
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DOI：
10.1016/j.jmb.2007.05.064
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发表时间：
2007-08-17
影响因子：
5.6
通讯作者：
Krengel, Ute
中科院分区：
文献类型：
--
作者：
Holmner, Asa;Askarieh, Glareh;Krengel, Ute
在许多细菌感染中，如幽门螺杆菌、空肠弯曲杆菌和霍乱弧菌感染，已经观察到疾病严重程度与感染个体的血型表型之间的相关性。在目前的调查中，我们研究了这种作用的分子基础的肠致病性大肠杆菌（ETEC）感染。ETEC是非侵入性细菌，通过第二信使途径引起腹泻。已经表明，来自人分离株的ETEC的主要毒力因子，即人不耐热肠毒素（hLT），识别某些血型表位，尽管血型抗原识别的分子基础尚不清楚。hLT的受体结合B亚基与血型A抗原类似物GalNAc α 3（Fuc α-2）Gal β 4（Fuc α-3）Glc β复合的2.5埃晶体结构提供了天然毒素中先前未知的结合位点的证据。该结构揭示了血型抗原识别背后的分子相互作用，并表明该蛋白质如何区分不同的血型表位。这些结果支持了先前争论的hLT在ETEC感染的血型依赖性中的作用。还讨论了有关霍乱弧菌感染中密切相关的霍乱毒素的类似观察结果。(c)2007爱思唯尔有限公司版权所有。
In a number of bacterial infections, such as Helicobacter pylori, Campylobacter jejuni and Vibrio cholerae infections, a correlation between the severity of disease and blood group phenotype of infected individuals has been observed. In the present investigation, we have studied the molecular basis of this effect for enterotoxigenic Escherichia coli (ETEC) infections. ETEC are non-invasive bacteria, which act through second messenger pathways to cause diarrhea. It has been suggested that the major virulence factor of ETEC from human isolates, i.e. the human heat-labile enterotoxin (hLT), recognizes certain blood group epitopes, although the molecular basis of blood group antigen recognition is unknown. The 2.5 angstrom crystal structure of the receptor-binding B-subunit of hLT in complex with the blood group A antigen analog GalNAc alpha 3(Fuc alpha-2)Gal beta 4(Fuc alpha-3)Glc beta provides evidence of a previously unknown binding site in the native toxin. The structure reveals the molecular interactions underlying blood group antigen recognition and suggests how this protein can discriminate between different blood group epitopes. These results support the previously debated role of hLT in the blood group dependence of ETEC infections. Similar observations regarding the closely related cholera toxin in V. cholera infections are also discussed. (c) 2007 Elsevier Ltd. All rights reserved.