Chemical Biology Graduate Program, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
Biochemistry. 2012 Jun 19;51(24):4800-6. doi: 10.1021/bi300592c. Epub 2012 Jun 8.
Gram-negative bacteria are impervious to many drugs and environmental stresses because they possess an outer membrane (OM) containing lipopolysaccharide (LPS). LPS is biosynthesized at the cytoplasmic (inner) membrane and is transported to the OM by an unknown mechanism involving the LPS transport proteins, LptA-G. These proteins have been proposed to form a bridge between the two membranes; however, it is not known how this bridge is assembled to prevent mistargeting of LPS. We use in vivo photo-cross-linking to reveal the specific protein-protein interaction sites that give rise to the Lpt bridge. We also show that the formation of this transenvelope bridge cannot proceed before the correct assembly of the LPS translocon in the OM. This ordered sequence of events may ensure that LPS is never transported to the OM if it cannot be translocated across it to the cell surface.
革兰氏阴性菌对许多药物和环境压力具有抵抗力，因为它们具有含有脂多糖（LPS）的外膜（OM）。 LPS 在细胞质（内膜）中生物合成，并通过涉及 LPS 转运蛋白 LptA-G 的未知机制转运到 OM。这些蛋白被提议形成两个膜之间的桥梁；然而，尚不清楚如何组装此桥以防止 LPS 错误靶向。我们使用体内光交联来揭示导致 Lpt 桥的特定蛋白质-蛋白质相互作用位点。我们还表明，在 OM 中 LPS 转位器的正确组装之前，无法进行这种跨膜桥的形成。这些事件的有序序列可能确保如果 LPS 不能穿过它转运到细胞表面，则永远不会被转运到 OM。
