败血梭菌α毒素的激活与作用机制

Activation and mechanism of Clostridium septicum alpha toxin.

作者信息

Ballard J, Sokolov Y, Yuan W L, Kagan B L, Tweten R K

机构信息

Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.

出版信息

Mol Microbiol. 1993 Nov;10(3):627-34. doi: 10.1111/j.1365-2958.1993.tb00934.x.

DOI:10.1111/j.1365-2958.1993.tb00934.x

PMID:7968539

Abstract

Clostridium septicum produces a single lethal factor, alpha toxin (AT), which is a cytolytic protein with a molecular mass of approximately 48 kDa. The 48 kDa toxin was found to be an inactive protoxin (ATpro) which could be activated via a carboxy-terminal cleavage with trypsin. The cleavage site was located approximately 4 kDa from the carboxy-terminus. Proteolytically activated ATpro had a specific activity of approximately 1.5 x 10(6) haemolytic units mg-1. The trypsin-activated toxin (ATact) was haemolytic, stimulated a prelytic release of potassium ions from erythrocytes which was followed by haemoglobin release, induced channel formation in planar membranes and aggregated into a complex of M(r) > 210,000 on erythrocyte membranes. ATpro did not exhibit these properties. ATact formed pores with a diameter of at least 1.3-1.6 nm. We suggest that pore formation on target cell membranes is responsible for the cytolytic activity of alpha toxin.

摘要

败血梭菌产生一种单一的致死因子，即α毒素（AT），它是一种分子量约为48 kDa的细胞溶解蛋白。发现48 kDa的毒素是一种无活性的前毒素（ATpro），可通过用胰蛋白酶进行羧基末端切割而被激活。切割位点位于距羧基末端约4 kDa处。经蛋白水解激活的ATpro具有约1.5×10⁶溶血单位mg⁻¹的比活性。胰蛋白酶激活的毒素（ATact）具有溶血作用，刺激红细胞提前释放钾离子，随后释放血红蛋白，在平面膜中诱导通道形成，并在红细胞膜上聚合成分子量大于210,000的复合物。ATpro不具有这些特性。ATact形成直径至少为1.3 - 1.6 nm的孔。我们认为靶细胞膜上的孔形成是α毒素细胞溶解活性的原因。