ANTHRAX TOXIN - CHANNEL-FORMING ACTIVITY OF PROTECTIVE ANTIGEN IN PLANAR PHOSPHOLIPID-BILAYERS

ANTHRAX TOXIN - CHANNEL-FORMING ACTIVITY OF PROTECTIVE ANTIGEN IN PLANAR PHOSPHOLIPID-BILAYERS
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DOI:
10.1073/pnas.86.7.2209
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发表时间:
1989-04-01
影响因子:
11.1
通讯作者:
FINKELSTEIN, A
FINKELSTEIN, A
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BLAUSTEIN, RO;KOEHLER, TM;FINKELSTEIN, A

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炭疽毒素由三种不同的蛋白质组成:保护性抗原(PA)、水肿因子(EF)和致死因子(LF),它们以二元组合的形式在实验动物中产生两种不同的反应:水肿(PA + EF)和死亡(PA + LF)。PA被认为与膜受体相互作用,并在蛋白水解加工后介导内吞作用和随后EF或LF易位到胞质溶胶中。在温和的胰蛋白酶解后,PA可以分离成两个片段,PA 65(65 kDa)和PA 20(20 kDa)。我们证明,胰蛋白酶裂解的PA能够在平面磷脂双层膜中形成阳离子选择性通道,并且这种活性仅限于PA 65片段; PA 20,LF和EF缺乏通道形成活性。这些PA 65通道表现出pH依赖性和电压依赖性的活性。sbd.一个属性让人想起由双链蛋白白喉,破伤风,和肉毒杆菌毒素形成的通道。
The three separate proteins that make up anthrax toxin.sbd.protective antigen (PA), edema factor (EF), and lethal factor (LF).sbd.act in binary combinations to produce two distinct reactions in experimental animals: edema (PA + EF) and death (PA + LF). PA is believed to interact with a membrane receptor, and after proteolytic processing, to mediate endocytosis and subsequent translocation of EF or LF into the cytosol. PA can be separated, after mild trypsinolysis, into two fragments, PA65 (65 kDa) and PA20 (20 kDa). We demonstrate that trypsin-cleaved PA is capable of forming cation- selective channels in planar phospholipid bilayer membranes and that this activity is confined to the PA65 fragment; PA20, LF, and EF are devoid of channel-forming activity. These PA65 channels exhibit pH-dependent and voltage-dependent activity.sbd.a property reminiscent of the channels formed by the two-chain proteins diphtheria, tetanus, and botulinum toxins.