Interaction of Clostridium perfringensIota-Toxin with Lipid Bilayer Membranes

Interaction of Clostridium perfringensIota-Toxin with Lipid Bilayer Membranes
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产气荚膜梭菌毒素与脂质双层膜的相互作用

DOI:
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发表时间:
2002
影响因子:
4.8
通讯作者:
M. Popoff
M. Popoff
中科院分区:
生物学2区
文献类型:
--
作者:
O. Knapp;R. Benz;M. Gibert;J. Marvaud;M. Popoff

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本文详细研究了产气荚膜梭菌ADP-核糖化毒素结合组分(Ib)与模型脂膜的相互作用。IB必须被胰酶激活才能在人工脂双层中形成通道。在1mKCl中,Ib容易形成的通道具有约85皮西姆的小的单通道电导。在单通道和多通道实验中,通道功能被酶组分Ia以pH依赖的方式阻断。只有当pH至少降低到5.6时,Ia介导的Ib才会发生强烈的通道阻断。单通道电导与KCl体水溶液浓度呈线性关系,表明通道性质更具一般性而非特异性。零电流膜电位测量表明,Ib通道对钾离子的通透性是对氯离子通透性的6倍∼。水相中不同迁移率的阳离子和阴离子组成的盐的选择性比发生了变化,再次表明Ib形成了一个充满水的总扩散孔。活化的Ib与脂类双层膜的不对称加成导致了不对称的电压依赖关系,表明其在膜内完全定向。氯喹和不同四烷基铵离子的滴定实验表明,这些化合物阻断了Ib通道,但对它们的亲和力很弱。使用Vero细胞进行的活体测量表明,氯喹和相关分子也不能有效地阻止碘毒素对细胞的中毒。讨论了Ib在IOTA-毒素跨靶细胞膜转运中的可能作用。
The interaction between model lipid membranes and the binding component (Ib) of the ADP-ribosylating iota-toxin ofClostridium perfringens was studied in detail. Ib had to be activated by trypsin to result in channel formation in artificial lipid bilayers. The channels formed readily by Ib had a small single-channel conductance of about 85 picosiemens in 1 m KCl. Channel function was blocked in single-channel and multichannel experiments by the enzymatic component Ia in a pH-dependent manner. The strong Ia-mediated channel block of Ib occurred only when the pH was at least lowered to pH 5.6. The single-channel conductance showed a linear dependence on the bulk aqueous KCl concentration, which indicated that the channel properties were more general than specific. Zero current membrane potential measurements suggested the Ib channel has an ∼6-fold higher permeability for potassium ions than for chloride. The selectivity ratio changed for salts composed of cations and anions of different mobility in the aqueous phase, again suggesting that Ib formed a water-filled general diffusion pore. Asymmetric addition of activated Ib to lipid bilayer membranes resulted in an asymmetric voltage dependence, indicating its full orientation within the membrane. Titration experiments with chloroquine and different tetraalkylammonium ions suggested that the Ib channel was blocked by these compounds but had only a weak affinity to them. In vivo measurements using Vero cells demonstrate that chloroquine and related molecules also did not efficiently block intoxication of the cells by iota-toxin. The possible role of Ib in the translocation of iota-toxin across the target cell membrane is discussed.
具有 ADP-核糖基转移酶活性的二元毒素的细胞和分子作用。
DOI: 10.1016/0041-0101(91)90076-4
发表时间: 1991
期刊: Toxicon : official journal of the International Society on Toxinology
影响因子: --
作者:
Considine,RV;Simpson,LL
通讯作者: Simpson,LL
DOI: 10.1073/pnas.86.7.2209
发表时间: 1989-04-01
影响因子: 11.1
作者:
BLAUSTEIN, RO;KOEHLER, TM;FINKELSTEIN, A
通讯作者: FINKELSTEIN, A
肉毒杆菌产生的二元毒素通过受体介导的内吞作用进入细胞发挥药理作用。
DOI: --
发表时间: 1989
期刊: The Journal of pharmacology and experimental therapeutics
影响因子: --
作者:
Simpson,LI
通讯作者: Simpson,LI
DOI: 10.1073/pnas.78.8.4950
发表时间: 1981-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
KAGAN, BL;FINKELSTEIN, A;COLOMBINI, M
通讯作者: COLOMBINI, M