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New insights into the tetrameric family of the Fur metalloregulators.
Biometals ( IF 3.5 ) Pub Date : 2019-06-04 , DOI: 10.1007/s10534-019-00201-8
S Nader 1 , J Pérard 1 , P Carpentier 1 , L Arnaud 1 , S Crouzy 1 , I Michaud-Soret 1
Affiliation  

The ferric uptake regulator (Fur) belongs to the family of the metal-responsive transcriptional regulators. Fur is a global regulator found in all proteobacteria. It controls the transcription of a wide variety of genes involved in iron metabolism but also in oxidative stress or virulence factor synthesis. As a general view, Fur proteins were considered to be dimeric proteins both in solution and when bound to DNA. However, our recent data demonstrate that Fur proteins can be classified into two subfamilies, according to their quaternary structure. The group of dimers is represented by E. coli, V. cholerae and Y. pestis Fur and the group of highly stable tetramers by P. aeruginosa and F. tularensis Fur. Here, another tetrameric structure of a PaFur mutant containing manganese and zinc metal ions is described. Through biochemical, structural and computational studies, we have deciphered the important structural characteristics of the tetramers and studied the main interactions responsible for their strength. Potential or mean force calculations for tetramer formation have been determinant to quantify these interactions. Moreover calculations allow us to propose that some conserved residues prevent the tetramerization in the subfamily of dimeric Fur.

中文翻译:

对Fur金属调节剂四聚体家族的新见解。

铁摄取调节剂(Fur)属于金属反应性转录调节剂家族。毛皮是所有蛋白杆菌中的全球调节剂。它控制着与铁代谢有关的各种基因的转录,也与氧化应激或毒力因子的合成有关。通常认为,Fur蛋白在溶液中和与DNA结合时都是二聚体蛋白。然而,我们最近的数据表明,根据其四级结构,Fur蛋白可以分为两个亚家族。二聚体的组由大肠杆菌,霍乱弧菌和鼠疫耶尔森氏菌代表,而高度稳定的四聚体的组由铜绿假单胞菌和土拉弗朗西斯科菌代表。在此,描述了含有锰和锌金属离子的PaFur突变体的另一种四聚体结构。通过生化,在结构和计算研究中,我们破译了四聚体的重要结构特征,并研究了造成其强度的主要相互作用。四聚体形成的势力或平均力计算已决定了这些相互作用的定量。此外,通过计算,我们可以提出一些保守的残基阻止了二聚体Fur的亚家族的四聚化。
更新日期:2019-11-01
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