Distinct mechanisms for K+ efflux, intoxication, and hemolysis by Bordetella pertussis AC toxin
Distinct mechanisms for K+ efflux, intoxication, and hemolysis by Bordetella pertussis AC toxin
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DOI：
10.1074/jbc.273.29.18260
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发表时间：
1998-07-17
影响因子：
4.8
通讯作者：
Hewlett, E
中科院分区：
文献类型：
--
作者：
Gray, M;Szabo, G;Hewlett, E
来自百日咳博德特氏菌的腺苷酸环化酶（AC）毒素将其催化结构域递送至靶细胞内部，在该靶细胞内部，其在称为中毒的过程中将宿主ATP转化为cAMP。该毒素还通过推测包括孔形成和渗透溶解的机制使绵羊红细胞溶血。中毒和溶血在明显不同的毒素浓度下出现，并在不同的时间尺度上演变，表明可能涉及不同的分子过程。本研究旨在验证中毒和溶血通过不同机制发生的假设，尽管AC毒素的溶血活性具有> 1h的滞后，但中毒立即开始。由于这种差异，我们寻找导致溶血的替代或前驱病变，并且从用其他成孔毒素处理的红细胞中观察到钾流出，AC毒素导致绵羊红细胞和Jurkat细胞（一种人T细胞白血病细胞系）的K+流出增加，该细胞在毒素添加后几分钟内出现。毒素浓度依赖性沿着时程分析表明毒素单体足以引发K+释放并将催化结构域递送至细胞内部。另一方面，溶血是一种高度协同的事件，可能需要这些个体单位随后的寡聚化。虽然Kf外排的诱导与中毒和溶血两者具有一些结构和环境要求，但它可以在中毒减少或预防的条件下发生。本文提供的数据表明，K+释放的跨膜途径与中毒所需的结构不同，但可能与最终导致溶血的结构相关或为溶血的前体。
Adenylate cyclase (AC) toxin from Bordetella pertussis delivers its catalytic domain to the interior of target cells where it converts host ATP to cAMP in a process referred to as intoxication. This toxin also hemolyzes sheep erythrocytes by a mechanism presumed to include pore formation and osmotic lysis, Intoxication and hemolysis appear at strikingly different toxin concentrations and evolve over different time scales, suggesting that different molecular processes may be involved. The present study was designed to test the hypothesis that intoxication and hemolysis occur by distinct mechanisms.Although the hemolytic activity of AC toxin has a lag of >1 h, intoxication starts immediately. Because of this difference, we sought a surrogate or precursor lesion that leads to hemolysis, and potassium efflux has been observed from erythrocytes treated with Other pore-forming toxins, AC toxin elicits an increase in K+ efflux from sheep erythrocytes and Jurkat cells, a human T-cell leukemia line, that beans within minutes of toxin addition. The toxin concentration dependence along with the analysis of the time course suggest that toxin monomers are sufficient to elicit release of K+ and to deliver the catalytic domain to the cell interior. Hemolysis, on the other hand, is a highly cooperative event that Likely requires a subsequent oligomerization of these individual units. Although induction of Kf efflux shares some structural and environmental requirements with both intoxication and hemolysis, it can occur under conditions in which intoxication is reduced or prevented. The data presented here suggest that the transmembrane pathway by which K+ is released is separate and distinct from the structure required for intoxication but may be related to, or a precursor of, that which is ultimately responsible for hemolysis.