Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA; Biological and Biomedical Sciences Program, Harvard University, Cambridge, MA 02138, USA.
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Curr Opin Struct Biol. 2020 Aug;63:26-33. doi: 10.1016/j.sbi.2020.03.005. Epub 2020 Apr 23.
Gram-negative bacteria possess a dual-membrane envelope, which provides defense against environmental assault, as well as formidable resistance against antibiotics. Lipopolysaccharide (LPS) is the primary lipid component in the outermost membrane leaflet of most Gram-negative bacteria, and plays critical roles in cell envelope formation. Newly synthesized LPS at the cytoplasmic side of the inner membrane is flipped across the inner membrane and pushed across the periplasm by two ATP-binding cassette transporters, MsbA and LptBFGC, respectively. Both transporters represent promising targets for developing new classes of antibiotics. In this review, we discuss recent advances in understanding the mechanism of LPS translocation driven by MsbA and LptBFGC, with a particular focus on new findings from structural studies.
革兰氏阴性菌具有双层膜包膜,为其提供了抵御环境侵袭的防御能力,同时对抗生素也具有强大的耐药性。脂多糖(LPS)是大多数革兰氏阴性菌最外层膜小叶的主要脂质成分,在细胞包膜形成中起着关键作用。在内膜的细胞质侧新合成的 LPS 被两个 ATP 结合盒转运蛋白(MsbA 和 LptBFGC)翻转穿过内膜,并分别通过它们推动穿过周质。这两种转运蛋白都代表了开发新型抗生素的有前途的靶点。在这篇综述中,我们讨论了理解 MsbA 和 LptBFGC 驱动 LPS 易位机制的最新进展,特别关注结构研究的新发现。