Crystal structures of a multidrug transporter reveal a functionally rotating mechanism
Crystal structures of a multidrug transporter reveal a functionally rotating mechanism
复制标题
DOI：
10.1038/nature05076
复制
发表时间：
2006-09-14
期刊：
影响因子：
64.8
通讯作者：
Yamaguchi, Akihito
中科院分区：
文献类型：
--
作者：
Murakami, Satoshi;Nakashima, Ryosuke;Yamaguchi, Akihito
AcrB 是大肠杆菌中主要的多药物外排转运蛋白，与外膜通道 TolC 和膜融合蛋白 AcrA 合作。在这里，我们描述了有基底和无基底的 AcrB 的晶体结构。 AcrB - 药物复合物由三个原聚体组成，每个原聚体具有不同的构象，对应于转运循环的三种功能状态之一。在三个原聚体之一的周质结构域中发现了结合的底物。大量的结合口袋是芳香的并且允许多位点结合。这些结构表明药物通过三步功能旋转机制输出，其中底物经历有序的结合变化。
AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB - drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change.