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首页> 外文期刊>Infection and immunity >Identification of a Receptor-Binding Region within Domain 4 of the Protective Antigen Component of Anthrax Toxin
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Identification of a Receptor-Binding Region within Domain 4 of the Protective Antigen Component of Anthrax Toxin

机译：炭疽毒素保护性抗原成分的结构域4内受体结合区的鉴定

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Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin, whereas PA is the receptor-binding component. To identify residues of PA that are involved in interaction with the cellular receptor, two solvent-exposed loops of domain 4 of PA (amino acids [aa] 679 to 693 and 704 to 723) were mutagenized, and the altered proteins purified and tested for toxicity in the presence of LF. In addition to the intended substitutions, novel mutations were introduced by errors that occurred during PCR. Substitutions within the large loop (aa 704 to 723) had no effect on PA activity. A mutated protein, LST-35, with three substitutions in the small loop (aa 679 to 693), bound weakly to the receptor and was nontoxic. A mutated protein, LST-8, with changes in three separate regions did not bind to receptor and was nontoxic. Toxicity was greatly decreased by truncation of the C-terminal 3 to 5 aa, but not by their substitution with nonnative residues or the extension of the terminus with nonnative sequences. Comparison of the 28 mutant proteins described here showed that the large loop (aa 704 to 722) is not involved in receptor binding, whereas residues in and near the small loop (aa 679 to 693) play an important role in receptor interaction. Other regions of domain 4, in particular residues at the extreme C terminus, appear to play a role in stabilizing a conformation needed for receptor-binding activity.
机译：炭疽芽孢杆菌的炭疽毒素是由致死因子（LF），浮肿因子（EF）和保护性抗原（PA）组成的三组分毒素。 LF和EF是毒素的催化成分，而PA是受体结合成分。为了鉴定参与与细胞受体相互作用的PA残基，诱变了PA结构域4的两个溶剂暴露的环（氨基酸[aa] 679至693和704至723），并对改变的蛋白质进行纯化并测试在LF存在下的毒性。除了预期的替代，PCR期间发生的错误还引入了新的突变。大环内（aa 704至723）的取代对PA的活性没有影响。一种突变蛋白LST-35，在小环中有三个取代基（aa 679至693），与受体的结合较弱，并且是无毒的。在三个独立区域发生变化的突变蛋白LST-8不与受体结合，并且是无毒的。通过将C末端3到5 aa截短，可大大降低毒性，但不会被非天然残基取代或末端被非天然序列延长。比较此处描述的28种突变蛋白显示，大环（aa 704至722）不参与受体结合，而小环（aa 679至693）中和附近的残基在受体相互作用中起重要作用。结构域4的其他区域，特别是极端C末端的残基，似乎在稳定受体结合活性所需的构象方面起作用。

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