Valeva A, Schnabel R, Walev I, Boukhallouk F, Bhakdi S, Palmer M
Institute of Medical Microbiology and Hygiene, University of Mainz, Obere Zahlbacher Strasse 67, D55101 Mainz, Germany.
J Biol Chem. 2001 May 4;276(18):14835-41. doi: 10.1074/jbc.M100301200. Epub 2001 Feb 2.
Staphylococcal alpha-toxin forms heptameric pores on eukaryotic cells. After binding to the cell membrane in its monomeric form, the toxin first assembles into a heptameric pre-pore. Subsequently, the pre-pore transforms into the final pore by membrane insertion of an amphipathic beta-barrel, which comprises the "central loop" domains of all heptamer subunits. The process of membrane insertion was analyzed here using a set of functionally altered toxin mutants. The results show that insertion may be initiated within an individual protomer when its NH2 terminus activates its central loop. The activated state is then shared with the central loops of the residual heptamer subunits, which results in cooperative membrane penetration. This cooperation of the central loops commences while these are still remote from the lipid bilayer. Nevertheless, it is subject to modulation by the target membrane, which therefore acts across a distance much like an allosteric effector. However, while allosteric transitions usually are reversible, membrane insertion of alpha-toxin is an irreversible event, and we show here that it can proceed to completion in a domino-like fashion when triggered by as little as a single foreign atom within the entire heptamer.
葡萄球菌α毒素在真核细胞上形成七聚体孔道。该毒素以单体形式与细胞膜结合后，首先组装成七聚体前体孔道。随后，前体孔道通过两亲性β桶插入细胞膜而转变为最终孔道，两亲性β桶由所有七聚体亚基的“中央环”结构域组成。本文使用一组功能改变的毒素突变体分析了膜插入过程。结果表明，当单个原体的NH2末端激活其中央环时，插入可能在该原体内部启动。然后，激活状态与其余七聚体亚基的中央环共享，从而导致协同的膜穿透。中央环的这种协同作用在它们仍远离脂质双层时就开始了。然而，它受到靶膜的调节，因此靶膜的作用就像变构效应剂一样跨越一定距离。然而，虽然变构转变通常是可逆的，但α毒素的膜插入是一个不可逆的事件，并且我们在此表明，当整个七聚体中只有一个外来原子触发时，它可以以多米诺骨牌的方式进行到底。
