Ternary structure of the outer membrane transporter FoxA with resolved signalling domain provides insights into TonB-mediated siderophore uptake
Ternary structure of the outer membrane transporter FoxA with resolved signalling domain provides insights into TonB-mediated siderophore uptake
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DOI：
10.7554/elife.48528
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发表时间：
2019-08-06
期刊：
影响因子：
7.7
通讯作者：
Tidow, Henning
中科院分区：
文献类型：
--
作者：
Josts, Inokentijs;Veith, Katharina;Tidow, Henning
许多微生物和真菌通过合成和分泌称为铁载体的高亲和力螯合剂来获得必需离子Fe 3+。在革兰氏阴性细菌中，这些铁载体复合物被位于细菌外膜（OM）中的高度特异性TonB依赖性转运蛋白（TBDT）积极吸收。然而，内膜蛋白TonB如何连接到OM中的转运蛋白以及铁载体和TonB与转运蛋白结合之间的相互作用的详细机制仍然知之甚少。在这里，我们提出了三种晶体结构的TBDT FoxA从铜绿假单胞菌（含有信号结构域）在复杂的铁载体ferrioxamine B和TonB和联合收割机结合常数的详细分析。的结构表明，铁载体和TonB-结合需要形成一个两步TonB-结合机制中的FoxA转运蛋白的易位能力状态。复杂的结构还表明TonB结合如何影响信号传导结构域的方向。
Many microbes and fungi acquire the essential ion Fe3+ through the synthesis and secretion of high-affinity chelators termed siderophores. In Gram-negative bacteria, these ferricsiderophore complexes are actively taken up using highly specific TonB-dependent transporters (TBDTs) located in the outer bacterial membrane (OM). However, the detailed mechanism of how the inner-membrane protein TonB connects to the transporters in the OM as well as the interplay between siderophore- and TonB-binding to the transporter is still poorly understood. Here, we present three crystal structures of the TBDT FoxA from Pseudomonas aeruginosa (containing a signalling domain) in complex with the siderophore ferrioxamine B and TonB and combine them with a detailed analysis of binding constants. The structures show that both siderophore and TonB-binding is required to form a translocation-competent state of the FoxA transporter in a two-step TonB-binding mechanism. The complex structure also indicates how TonB-binding influences the orientation of the signalling domain.