Ruiz Natividad, Gronenberg Luisa S, Kahne Daniel, Silhavy Thomas J
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5537-42. doi: 10.1073/pnas.0801196105. Epub 2008 Mar 28.
The outer membrane (OM) of most Gram-negative bacteria contains lipopolysaccharide (LPS) in the outer leaflet. LPS, or endotoxin, is a molecule of important biological activities. In the host, LPS elicits a potent immune response, while in the bacterium, it plays a crucial role by establishing a barrier to limit entry of hydrophobic molecules. Before LPS is assembled at the OM, it must be synthesized at the inner membrane (IM) and transported across the aqueous periplasmic compartment. Much is known about the biosynthesis of LPS but, until recently, little was known about its transport and assembly. We applied a reductionist bioinformatic approach that takes advantage of the small size of the proteome of the Gram-negative endosymbiont Blochmannia floridanus to search for novel factors involved in OM biogenesis. This led to the discovery of two essential Escherichia coli IM proteins of unknown function, YjgP and YjgQ, which are required for the transport of LPS to the cell surface. We propose that these two proteins, which we have renamed LptF and LptG, respectively, are the missing transmembrane components of the ABC transporter that, together with LptB, functions to extract LPS from the IM en route to the OM.
大多数革兰氏阴性菌的外膜在外层小叶中含有脂多糖(LPS)。LPS,即内毒素,是一种具有重要生物学活性的分子。在宿主体内,LPS引发强烈的免疫反应,而在细菌中,它通过建立一道屏障来限制疏水分子的进入,从而发挥关键作用。在LPS在外膜组装之前,它必须在内膜(IM)上合成并穿过水性周质区室进行转运。关于LPS的生物合成我们已经了解很多,但直到最近,对其转运和组装却知之甚少。我们采用了一种简化的生物信息学方法,利用革兰氏阴性内共生菌佛罗里达布洛赫曼氏菌蛋白质组规模较小的特点,来寻找参与外膜生物合成的新因子。这导致发现了两种功能未知的大肠杆菌内膜必需蛋白YjgP和YjgQ,它们是LPS转运至细胞表面所必需的。我们提出,这两种蛋白我们分别将其重新命名为LptF和LptG,是ABC转运蛋白中缺失的跨膜组分,它们与LptB一起,在LPS从内膜转运至外膜的过程中发挥从内膜提取LPS的作用。