Kuk Alvin C Y, Mashalidis Ellene H, Lee Seok-Yong
Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina, USA.
Nat Struct Mol Biol. 2017 Feb;24(2):171-176. doi: 10.1038/nsmb.3346. Epub 2016 Dec 26.
Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is flipping of the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into PG. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, understanding of how MurJ flips lipid II, and of how MOP transporters operate in general, remains limited due to a lack of structural information. Here we present a crystal structure of MurJ from Thermosipho africanus in an inward-facing conformation at 2.0-Å resolution. A hydrophobic groove is formed by two C-terminal transmembrane helices, which leads into a large central cavity that is mostly cationic. Our studies not only provide the first structural glimpse of MurJ but also suggest that alternating access is important for MurJ function, which may be applicable to other MOP superfamily transporters.
肽聚糖（PG）保护细菌免受渗透压裂解，其生物合成是关键的抗生素作用靶点。PG生物合成的一个核心步骤是脂质连接的PG前体脂质II翻转穿过细胞质膜，随后掺入PG中。MurJ是多药/寡糖基脂质/多糖（MOP）转运蛋白超家族的一部分，最近被证明可执行这一过程。然而，由于缺乏结构信息，对MurJ如何翻转脂质II以及MOP转运蛋白一般如何运作的了解仍然有限。在此，我们展示了来自非洲嗜热栖热菌的MurJ处于向内构象时2.0 Å分辨率的晶体结构。一个疏水凹槽由两个C端跨膜螺旋形成，通向一个大多为阳离子的大中央腔。我们的研究不仅首次提供了MurJ的结构视图，还表明交替式通道对MurJ的功能很重要，这可能适用于其他MOP超家族转运蛋白。
