Dominant-negative mutants of a toxin subunit: An approach to therapy of anthrax

被引:159
|
作者
Sellman, BR [1 ]
Mourez, M [1 ]
Collier, RJ [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA
关键词
D O I
10.1126/science.109563
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The protective antigen moiety of anthrax toxin translocates the toxin's enzymic moieties to the cytosol of mammalian cells by a mechanism that depends on its ability to heptamerize and insert into membranes. We identified dominant-negative mutants of protective antigen that co-assemble with the wild-type protein and block its ability to translocate the enzymic moieties across membranes. These mutants strongly inhibited toxin action in cell culture and in an animal intoxication model, suggesting that they could be useful in therapy of anthrax.
引用
收藏
页码:695 / 697
页数:3
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