Function of a novel SPFH domain protein in bacteria

细菌细胞被划分成不同的功能区域和结构域。这种区隔包括质膜。包括我的实验室在内的几个实验室的研究表明，支架蛋白（如flotillins）有助于将膜组织成功能域。此外，一些细胞过程也被认为依赖于这种膜区隔化，但精确的分子机制仍然相当难以捉摸。Flotillins共享一个被称为SPFH域的签名序列。该蛋白结构域存在于口蛋白、禁蛋白、flotillins和细菌HflK/C蛋白中。在所有情况下，SPFH结构域已被证明有助于蛋白质寡聚化，可能是作为分子支架功能的必要条件。近年来，对细菌flotillins的研究引起了极大的兴趣，因为flotillins组装的零突变或化学失活对细胞具有多效性，并导致生物膜形成和细胞生长和分化的功能受损。Flotillins专门与高度有序的膜结合，因此提出这些SPFH蛋白是所谓脂筏的标记蛋白。我们最近在枯草芽孢杆菌中发现了SPFH结构域蛋白家族的新成员。我们的初步工作表明，该蛋白定位于液体无序膜区域，并参与细胞应激反应。遗传和蛋白质组学分析揭示了这种新的SPFH蛋白与一般应激反应途径和细胞包膜应激的紧密联系。与flotillins不同，这个SPFH结构域蛋白不与质膜本身结合，但需要两个编码在同一操纵子中的膜整合蛋白。膜复合体仅在应激条件下组装，我们假设该复合体在细菌对外部细胞包膜应激的感知和反应中起着核心作用。

Bacterial cells are surprisingly compartmentalized into functional areas and domains. This compartmentalization includes the plasma membrane. Research from several laboratories, including mine, has shown that scaffold proteins such as flotillins help to organize the membrane into functional domains. Also several cellular processes are thought to rely on this membrane compartmentalization the precise molecular mechanisms are still rather elusive. Flotillins share a signature sequence that has been termed SPFH domain. This protein domain is found in stomatins, prohibitions, flotillins and the bacterial HflK/C proteins. In all cases the SPFH domain has been shown to contribute to protein oligomerization, likely a necessity to function as molecular scaffold. Research on bacterial flotillins has gained a tremendous interest in recent years because null mutations or chemical inactivation of flotillin assembly has pleiotropic effects on cells and leads to impaired functions in biofilm formation and cellular growth and differentiation. Flotillins exclusively associate with highly ordered membranes and hence it was proposed that these SPFH proteins are marker proteins for so-called lipid rafts. We have recently discovered a new member of the SPFH domain family of proteins in Bacillus subtilis. Our preliminary work revealed that this protein localizes to liquid disordered membrane regions and that it is involved in cellular stress response. Genetic and proteomic analyses revealed a tight link of this novel SPFH protein to the general stress response pathway and to cell envelope stress. Unlike flotillins, this SPFH domain protein does not bind to the plasma membrane itself, but requires tow membrane integral proteins that are encoded in the same operon. The membrane complex only assembles under stress conditions and we hypothesize that this complex plays a central role in the perception and response to external cell envelope stress in bacteria.