Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, Institute of Biomedicine, University of Gothenburg, Sweden.
Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Charles University, Faculty of Pharmacy in Hradec Králové, Akademika Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
Glycobiology. 2022 Apr 21;32(5):391-403. doi: 10.1093/glycob/cwab133.
The heat-labile enterotoxins of Escherichia coli and cholera toxin of Vibrio cholerae are related in structure and function. Each of these oligomeric toxins is comprised of one A polypeptide and five B polypeptides. The B-subunits bind to gangliosides, which are followed by uptake into the intoxicated cell and activation of the host's adenylate cyclase by the A-subunits. There are two antigenically distinct groups of these toxins. Group I includes cholera toxin and type I heat-labile enterotoxin of E. coli; group II contains the type II heat-labile enterotoxins of E. coli. Three variants of type II toxins, designated LT-IIa, LT-IIb and LT-IIc have been described. Earlier studies revealed the crystalline structure of LT-IIb. Herein the carbohydrate binding specificity of LT-IIc B-subunits was investigated by glycosphingolipid binding studies on thin-layer chromatograms and in microtiter wells. Binding studies using a large variety of glycosphingolipids showed that LT-IIc binds with high affinity to gangliosides with a terminal Neu5Acα3Gal or Neu5Gcα3Gal, e.g. the gangliosides GM3, GD1a and Neu5Acα3-/Neu5Gcα3--neolactotetraosylceramide and Neu5Acα3-/Neu5Gcα3-neolactohexaosylceramide. The crystal structure of LT-IIc B-subunits alone and with bound LSTd/sialyl-lacto-N-neotetraose d pentasaccharide uncovered the molecular basis of the ganglioside recognition. These studies revealed common and unique functional structures of the type II family of heat-labile enterotoxins.
大肠杆菌不耐热肠毒素和霍乱弧菌霍乱毒素在结构和功能上相关。这些聚合毒素中的每一种都由一个 A 多肽和五个 B 多肽组成。B 亚基与神经节苷脂结合，随后被摄入中毒细胞，A 亚基激活宿主的腺苷酸环化酶。这些毒素有两个抗原上不同的组。第 I 组包括霍乱毒素和大肠杆菌的 I 型不耐热肠毒素；第 II 组包含大肠杆菌的 II 型不耐热肠毒素。已经描述了三种 II 型毒素的变体，称为 LT-IIa、LT-IIb 和 LT-IIc。早期的研究揭示了 LT-IIb 的晶体结构。本文通过在薄层色谱和微量滴定孔中的糖脂结合研究，研究了 LT-IIc B 亚基的碳水化合物结合特异性。使用各种糖脂的结合研究表明，LT-IIc 与具有末端 Neu5Acα3Gal 或 Neu5Gcα3Gal 的神经节苷脂，例如 GM3、GD1a 和 Neu5Acα3-/Neu5Gcα3--新乳糖四糖神经酰胺和 Neu5Acα3-/Neu5Gcα3-新乳糖六糖神经酰胺，具有高亲和力结合。LT-IIc B 亚基单独和与结合的 LSTd/唾液酸乳糖-N-新四糖 d 五糖结合的晶体结构揭示了神经节苷脂识别的分子基础。这些研究揭示了不耐热肠毒素 II 型家族的共同和独特的功能结构。
