当前位置: X-MOL 学术Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Structural mechanism of phospholipids translocation by MlaFEDB complex.
Cell Research ( IF 44.1 ) Pub Date : 2020-09-03 , DOI: 10.1038/s41422-020-00404-6
Ximin Chi 1, 2 , Qiongxuan Fan 1, 2 , Yuanyuan Zhang 1, 2 , Ke Liang 1, 2 , Li Wan 1, 2 , Qiang Zhou 1, 2 , Yanyan Li 1, 2
Affiliation  

In Gram-negative bacteria, phospholipids are major components of the inner membrane and the inner leaflet of the outer membrane, playing an essential role in forming the unique dual-membrane barrier to exclude the entry of most antibiotics. Understanding the mechanisms of phospholipid translocation between the inner and outer membrane represents one of the major challenges surrounding bacterial phospholipid homeostasis. The conserved MlaFEDB complex in the inner membrane functions as an ABC transporter to drive the translocation of phospholipids between the inner membrane and the periplasmic protein MlaC. However, the mechanism of phospholipid translocation remains elusive. Here we determined three cryo-EM structures of MlaFEDB from Escherichia coli in its nucleotide-free and ATP-bound conformations, and performed extensive functional studies to verify and extend our findings from structural analyses. Our work reveals unique structural features of the entire MlaFEDB complex, six well-resolved phospholipids in three distinct cavities, and large-scale conformational changes upon ATP binding. Together, these findings define the cycle of structural rearrangement of MlaFEDB in action, and suggest that MlaFEDB uses an extrusion mechanism to extract and release phospholipids through the central translocation cavity.



中文翻译:

MlaFEDB复合物对磷脂易位的结构机制。

在革兰氏阴性菌中,磷脂是内膜和外膜内小叶的主要成分,在形成独特的双膜屏障以阻止大多数抗生素进入方面发挥着重要作用。了解内膜和外膜之间磷脂易位的机制是围绕细菌磷脂稳态的主要挑战之一。内膜中保守的 MlaFEDB 复合物作为 ABC 转运蛋白,驱动内膜和周质蛋白 MlaC 之间的磷脂易位。然而,磷脂易位的机制仍然难以捉摸。在这里,我们确定了来自大肠杆菌的 MlaFEDB 的三种冷冻电镜结构在其无核苷酸和 ATP 结合构象中,并进行了广泛的功能研究以验证和扩展我们从结构分析中的发现。我们的工作揭示了整个 MlaFEDB 复合物的独特结构特征、三个不同腔中的六种解析良好的磷脂,以及 ATP 结合后的大规模构象变化。总之,这些发现定义了 MlaFEDB 的结构重排循环,并表明 MlaFEDB 使用挤压机制通过中央易位腔提取和释放磷脂。

更新日期:2020-09-03
down
wechat
bug