Crystal structure of the MOP flippase MurJ in an inward-facing conformation.
Crystal structure of the MOP flippase MurJ in an inward-facing conformation.
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DOI：
10.1038/nsmb.3346
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发表时间：
2017-02
影响因子：
16.8
通讯作者：
Lee SY
中科院分区：
文献类型：
--
作者：
Kuk AC;Mashalidis EH;Lee SY
肽聚糖（PG）可保护细菌免遭渗透裂解，其生物发生是抗生素的关键靶点。 PG 生物合成的核心步骤是将脂质连接的 PG 前体脂质 II 翻转穿过细胞质膜，以便随后掺入肽聚糖中。 MurJ 是多药/寡糖脂/多糖 (MOP) 转运蛋白超家族的一部分，最近被证明可以执行这一过程。然而，由于缺乏结构信息，我们对 MurJ 如何翻转脂质 II 以及 MOP 转运蛋白如何一般运作的理解仍然受到限制。在这里，我们展示了来自 Thermosipho africanus 的 MurJ 晶体结构，其分辨率为 2.0 Å，呈向内构象。疏水沟由两个 C 端跨膜螺旋形成，通向一个主要为阳离子的大中央空腔。我们的研究不仅首次提供了 MurJ 的结构概览，而且表明交替通路对于 MurJ 功能很重要，这可能适用于其他 MOP 超家族转运蛋白。
Peptidoglycan (PG) protects bacteria from osmotic lysis, and its biogenesis is a key antibiotic target. A central step in PG biosynthesis is to flip the lipid-linked PG precursor lipid II across the cytoplasmic membrane for subsequent incorporation into peptidoglycan. MurJ, part of the multidrug/oligosaccharidyl-lipid/polysaccharide (MOP) transporter superfamily, was recently shown to carry out this process. However, our understanding of how MurJ flips lipid II and how MOP transporters operate in general remains limited by 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.