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首页> 外文期刊>The FEBS journal >Modular organisation of inducer recognition and allostery in the tetracycline repressor
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Modular organisation of inducer recognition and allostery in the tetracycline repressor

机译：四环素阻遏物中的诱导识别和仿生组织的模块化组织

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摘要

Induction of the tetracycline repressor (TetR) results from antibiotic-dependent changes in the relative positioning of the DNA-binding domains within the promoter-associated repressor dimer, but the key determinants of this allosteric effect remain poorly characterised. Intriguingly, previous mutational analyses of the tetracycline-interacting site revealed a lack of correlation between residual affinity and induction propensity, suggesting that some of the residues in contact with the antibiotic primarily act in ligand recognition and retention, whereas others are required to transmit the allosteric signal. Here, we provide a structural basis for these observations via crystallographic analysis of the point mutants N82A, H100A, T103A and E147A in complex with the inducer 5a, 6-anhydrotetracycline. In conjunction with the available functional data, the four structures demonstrate that a trigger-like movement of the region between helices alpha 6 and alpha 7 towards and into the binding site plays a decisive role in the intramolecular communication process. In sharp contrast, residues lining the binding cavity proper have little or no influence on the allosteric mechanism as such. This nearly complete physical separation of ligand recognition and allostery will have allowed diverging TetR-like repressors to bind novel effectors while the existing induction mechanism remained intact. Consequently, the modularity described here may have been a key factor in the evolutionary success of the widespread and highly diversified repressor class.
机译：四环素阻遏物（四）的诱导是由促进剂相关的阻遏物二聚体内DNA结合结构域的相对定位的抗生素依赖性变化，但这种变构效果的关键决定因素仍然是特征性差。有趣的是，四环素相互作用位点的先前突变分析揭示了残留亲和力和诱导倾向之间缺乏相关性，表明一些与抗生素接触的残留物主要在配体识别和保留中，而其他残留物在配体识别和保留中，则其他残留物在识别和保留中，其他残留物在识别和保留中，其他残留物主要用于传输变构件信号。在这里，我们通过点突变体N82A，H100A，T103A和E147A与诱导剂5A，6-ANHYDROTTRATYCLINE络合物的结晶分析提供这些观察结果的结构基础。结合可用的功能数据，四种结构表明，螺旋α6和α7之间区域的触发样运动朝向结合位点在分子内通信过程中起决定性作用。在鲜明的对比度下，衬里的残留物衬里适当对较少或没有对变构机制的影响。这种近乎完全的配体识别和仿生体的物理分离将使散发出衍生的抑制剂，以结合新的效果，而现有的感应机制保持完整。因此，这里描述的模块化可能是广泛和高度多样化的阻遏类进化成功的关键因素。

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