Structural Insights into the Lipid A Transport Pathway in MsbA
Structural Insights into the Lipid A Transport Pathway in MsbA
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DOI：
10.1016/j.str.2019.04.007
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发表时间：
2019-07-02
期刊：
影响因子：
5.7
通讯作者：
Zhang, Qinghai
中科院分区：
文献类型：
--
作者：
Padayatti, Pius S.;Lee, Sung Chang;Zhang, Qinghai
MsbA是革兰氏阴性菌中必需的atp结合盒转运体，可将脂质A和脂多糖从细胞质小叶转运到内膜的质周小叶。在这里，我们报道了鼠伤寒沙门氏菌MsbA在2.8埃分辨率下与脂质A共结晶并使用稳定的表面两亲性物质后的内向构象的x射线结构。该结构在跨膜门静脉中显示出一个振幅较大的开口，这可能是脂质a从其合成位点进入蛋白质封闭转运途径所必需的。在跨膜腔内进一步观察到假定的脂质A密度，与陷阱和翻转模型一致。额外的电子密度归因于脂质A在跨膜螺旋的质周末端的外表面裂缝附近被观察到。通过与现有MsbA结构的比较分析，这些发现为脂质A转运途径提供了新的结构见解。
MsbA is an essential ATP-binding cassette transporter in Gram-negative bacteria that transports lipid A and lipopolysaccharide from the cytoplasmic leaflet to the periplasmic leaflet of the inner membrane. Here we report the X-ray structure of MsbA from Salmonella typhimurium at 2.8-angstrom resolution in an inward-facing conformation after cocrystallization with lipid A and using a stabilizing facial amphiphile. The structure displays a large amplitude opening in the transmembrane portal, which is likely required for lipid A to pass from its site of synthesis into the protein-enclosed transport pathway. Putative lipid A density is observed further inside the transmembrane cavity, consistent with a trap and flip model. Additional electron density attributed to lipid A is observed near an outer surface cleft at the periplasmic ends of the transmembrane helices. These findings provide new structural insights into the lipid A transport pathway through comparative analysis with existing MsbA structures.