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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Two ligand-binding sites in the O_2-sensing signal transducer HemAT: Implications for ligand recognition/discrimination and signaling
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Two ligand-binding sites in the O_2-sensing signal transducer HemAT: Implications for ligand recognition/discrimination and signaling

机译：O_2传感信号传感器HemAT中的两个配体结合位点：对配体识别/区分和信号传导的影响

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摘要

We have identified a ligand (CO) accommodation cavity in the signal transducer sensor protein HemAT (heme-based aerotactic transducer) that allows us to gain single-molecule insights into the mechanism of gas sensor proteins. Specific mutations that are distal and proximal to the heme were designed to perturb the electrostatic field near the ligand that is bound to the heme and near the accommodated ligand in the cavity. We report the detection of a second site in heme proteins in which the exogenous ligand is accommodated in an internal cavity. The conformational gate that directs the ligand-migration pathway from the distal to the proximal site of the heme, where the ligand is trapped, has been identified. The data provide evidence that the heme pocket is the specific ligand trap and suggest that the regulatory mechanism may be tackled starting from more than one position in the protein. Based on the results, we propose a dynamic coupling between the two distinct binding sites as the underlying allosteric mechanism for gas recognition/discrimination that triggers a conformational switch for signaling by the oxygen sensor protein HemAT.
机译：我们已经在信号传感器蛋白HemAT（基于血红素的全顺性换能器）中鉴定了一个配体（CO）容纳腔，这使我们可以获得对气体传感器蛋白机理的单分子见解。将血红素远端和近端的特定突变设计为扰动与血红素结合的配体附近和腔中容纳的配体附近的静电场。我们报告了在血红素蛋白中的第二个位点的检测，其中外源性配体容纳在内部空腔中。已经确定了指导配体从血红素的远端到近端部位（配体被捕获）的近端迁移路径的构象门。数据提供了血红素口袋是特异性配体陷阱的证据，并表明调节机制可能是从蛋白质中的多个位置开始解决的。根据结果​​，我们提出了两个不同的结合位点之间的动态耦合，作为气体识别/区分的潜在变构机制，触发了由氧传感器蛋白HemAT发出信号的构象转换。

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