Cholera is an acute diarrheal disease caused by the bacterium Vibrio cholerae that still results in 20,000 to 140,000 deaths per year worldwide according to the World Health Organization. Once the bacterium reaches the small intestine after ingestion, it hangs on to the intestinal mucus and starts producing a proteinaceous multimeric toxin consisting of one catalytic A subunit and a pentamer of glycolipid-binding B subunits. This AB5 organization is shared by a family of bacterial toxins that includes the toxins of Bortadella pertussis, pathogenic strains of Escherichia coli, and Shigella dysenteriae. The mechanism of toxicity relies on the delivery of the catalytic A subunit to the cell via endocytosis mediated by the B subunit. This homopentameric B subunit itself is assembled into a pentagon shape that binds to the plasma membrane and carries the A subunit into cells, and the biophysical basis of cellular internalization of the cholera toxin is the topic of Kabbani et al. (1) in PNAS. Interestingly and abundantly exploited in the investigation of endocytic mechanisms, the B subunits of several AB5 toxins alone are capable of being endocytosed by themselves. They do so by binding to glycolipids in the plasma membrane in a pentameric arrangement of binding sites, which are spaced 3 nm apart. Such a pentavalent 3-nm spacing of binding sites to glycolipids is, interestingly, shared by polyomaviridae such as SV40 and the murine polyomavirus (2). Glycolipid-binding AB5 toxins and glycolipid-binding polyomaviridae can deform membranes in vitro and in energy-depleted cells (3, 4) and are internalized by clathrin-independent endocytosis (3, 5, 6). The unifying principle of this so far incompletely understood uptake pathway seems to be the reliance of extracellular ligands on binding to several tightly clustered carbohydrate moieties on …

中文翻译：

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霍乱毒素β亚基引起的膜变形需要多个结合位点。

霍乱是由霍乱弧菌引起的一种急性腹泻病，根据世界卫生组织的数据，全世界每年仍导致20,000至140,000人死亡。细菌在摄入后到达小肠后，便会挂在肠粘液上，并开始产生一种蛋白质多聚体毒素，该毒素由一个催化的A亚基和一个糖脂结合B亚基的五聚体组成。该AB5组织由细菌毒素家族共享，其中包括百日咳博德特氏菌，大肠杆菌的致病菌株和痢疾志贺氏菌的毒素。。毒性机制依赖于催化性A亚基通过B亚基介导的内吞作用向细胞的传递。该同五聚体B亚基本身被组装成五角形形状，该五角形形状与质膜结合并携带A亚基进入细胞，霍乱毒素的细胞内在化的生物物理基础是Kabbani等人的主题。（1）。有趣的是，在研究内吞机制中，只有几种AB5毒素的B亚基能够自身被内吞。它们通过以五聚体形式的结合位点与质膜中的糖脂结合而实现，结合位点的间隔为3 nm。有趣的是，这种多价的3 nm的糖脂结合位点间距是由多瘤病毒科（如SV40）和鼠类多瘤病毒共享的（2）。糖脂结合AB5毒素和糖脂结合多瘤病毒科可在体外和在能量耗尽的细胞变形膜（3，4），并通过网格蛋白的内吞作用的独立（内化3，5，6）。迄今为止，尚未完全理解的吸收途径的统一原理似乎是细胞外配体依赖于与……上几个紧密簇集的碳水化合物部分的结合。