Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG
Structural basis for lipopolysaccharide extraction by ABC transporter LptB2FG
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DOI：
10.1038/nsmb.3399
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发表时间：
2017-05-01
影响因子：
16.8
通讯作者：
Huang, Yihua
中科院分区：
文献类型：
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作者：
Luo, Qingshan;Yang, Xu;Huang, Yihua
在生物合成之后，细菌脂多糖（LPS）瞬时锚定到内膜（IM）的外小叶。ATP结合盒（ABC）转运蛋白LptB（2）FG从IM提取LPS分子并将其转运到外膜。在这里，我们报告的晶体结构的无核苷酸LptB（2）FG从铜绿假单胞菌。该结构揭示了脂多糖转运蛋白LptF和LptG各自含有跨膜结构域（TMD）、周质β-环糊精样结构域和在细胞质侧与LptB相互作用的偶联螺旋。LptF和LptG TMD在IM中形成一个大的外向V形腔。突变分析表明，LPS可以通过LptF和LptG的TMD结构域的界面侧向进入中央腔，并且在ATP结合和LptB水解后被排出到β-β-淀粉样结构域中。这些研究表明，LptB（2）FG提取LPS的机制与经典的ABC转运蛋白（通过IM转运底物）不同。
After biosynthesis, bacterial lipopolysaccharides (LPS) are transiently anchored to the outer leaflet of the inner membrane (IM). The ATP-binding cassette (ABC) transporter LptB(2)FG extracts LPS molecules from the IM and transports them to the outer membrane. Here we report the crystal structure of nucleotide-free LptB(2)FG from Pseudomonas aeruginosa. The structure reveals that lipopolysaccharide transport proteins LptF and LptG each contain a transmembrane domain (TMD), a periplasmic beta-jellyroll-like domain and a coupling helix that interacts with LptB on the cytoplasmic side. The LptF and LptG TMDs form a large outward-facing V-shaped cavity in the IM. Mutational analyses suggest that LPS may enter the central cavity laterally, via the interface of the TMD domains of LptF and LptG, and is expelled into the beta-jellyroll-like domains upon ATP binding and hydrolysis by LptB. These studies suggest a mechanism for LPS extraction by LptB(2)FG that is distinct from those of classical ABC transporters that transport substrates across the IM.