STAPHYLOCOCCAL ALPHA-TOXIN - OLIGOMERIZATION OF HYDROPHILIC MONOMERS TO FORM AMPHIPHILIC HEXAMERS INDUCED THROUGH CONTACT WITH DEOXYCHOLATE DETERGENT MICELLES
STAPHYLOCOCCAL ALPHA-TOXIN - OLIGOMERIZATION OF HYDROPHILIC MONOMERS TO FORM AMPHIPHILIC HEXAMERS INDUCED THROUGH CONTACT WITH DEOXYCHOLATE DETERGENT MICELLES
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DOI：
10.1073/pnas.78.9.5475
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
TRANUMJENSEN, J
中科院分区：
文献类型：
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作者：
BHAKDI, S;FUSSLE, R;TRANUMJENSEN, J
天然金黄色葡萄球菌α-毒素作为MW 34，000的亲水性多肽链分泌。在临界胶束浓度以上的脱氧胆酸盐的存在下，诱导毒素单体自缔合，形成环状或圆柱形的寡聚体。低聚物是两亲性的和结合的洗涤剂。在脱氧胆酸盐溶液中，蛋白质-去污剂复合物的沉降系数为10.4S。在沉降平衡时通过超离心分析确定MW为238，700。因为定量的去污剂结合研究表明蛋白质/去污剂的比例为apprx。5：1（wt/wt）时，每种蛋白质-去污剂复合物中的蛋白质部分被确定为MW 200，000，对应于天然分子的六聚体。两亲性毒素六聚体在超微结构上与在生物靶膜上和生物靶膜中形成的溶细胞环状毒素复合物无法区分。它们结合脂质，并可被纳入人工卵磷脂脂质囊泡。因此，毒素蛋白分子通过自缔合从亲水性单体到两亲性寡聚物的转变已被证明仅通过天然蛋白分子与适当的两亲性底物的接触是可诱导的。
Native Staphylococcus aureus .alpha.-toxin is secreted as a hydrophilic polypeptide chain of MW 34,000. The presence of deoxycholate above the critical micellar concentration induced the toxin monomers to self-associate, forming ring or cylindrical oligomers. The oligomers were amphiphilic and bound detergent. In deoxycholate solution, the protein-detergent complexes exhibited a sedimentation coefficient of 10.4 S. A MW of 238,700 was determined by ultracentrifugation analyses at sedimentation equilibrium. Because quantitative detergent-binding studies indicated a protein/detergent ratio of .apprx. 5:1 (wt/wt), the protein moiety in each protein-detergent complex was determined to be .apprx. MW 200,000, corresponding to a hexamer of the native molecule. The amphiphilic toxin hexamers were ultrastructurally indistinguishable from the cytolytic, annular toxin complexes that form on and in biological target membranes. They bound lipid and could be incorporated into artificial lecithin lipid vesicles. The transition of toxin protein molecules from a hydrophilic monomer to an amphiphilic oligometer through self-association has thus been shown to be inducible solely through contact of the native protein molecules with an appropriate amphiphilic substrate.