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Conserved Structure and Function in the Granulysin and NK-Lysin Peptide Family

机译:颗粒溶素和NK-赖氨酸肽家族中的保守结构和功能

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Granulysin and NK-lysin are homologous bactericidal proteins with a moderate residue identity (35%), both of which have antimycobacterial activity. Short loop peptides derived from the antimycobacterial domains of granulysin, NK-lysin, and a putative chicken NK-lysin were examined and shown to have comparable antimycobacterial but variable Escherichia coli activities. The known structure of the NK-lysin loop peptide was used to predict the structure of the equivalent peptides of granulysin and chicken NK-lysin by homology modeling. The last two adopted a secondary structure almost identical to that of NK-lysin. All three peptides form very similar three-dimensional (3-D) architectures in which the important basic residues assume the same positions in space. The basic residues in granulysin are arginine, while those in NK-lysin and chicken NK-lysin are a mixture of arginine and lysine. We altered the ratio of arginine to lysine in the granulysin fragment to examine the importance of basic residues for antimycobacterial activity. The alteration of the amino acids reduced the activity against E. coli to a larger extent than that against Mycobacterium smegmatis. In granulysin, the arginines in the loop structure are not crucial for antimycobacterial activity but are important for cytotoxicity. We suggest that the antibacterial domains of the related proteins granulysin, NK-lysin, and chicken NK-lysin have conserved their 3-D structure and their function against mycobacteria.
机译:颗粒溶素和NK-溶素是具有中等残基同一性(35%)的同源杀菌蛋白,两者均具有抗分枝杆菌活性。检查了来自颗粒溶素,NK-溶素和推定的鸡NK-溶素的抗分枝杆菌结构域的短环肽,它们具有可比的抗分枝杆菌活性,但具有可变的大肠杆菌活性。 NK-溶素环肽的已知结构用于通过同源性建模预测颗粒溶素和鸡NK-溶素的等效肽的结构。后两个采用的二级结构几乎与NK-溶素相同。所有这三种肽均形成非常相似的三维(3-D)结构,其中重要的基本残基在空间中的位置相同。颗粒溶素中的碱性残基是精氨酸,而NK-溶素和鸡肉NK-溶素中的残基是精氨酸和赖氨酸的混合物。我们更改了颗粒溶素片段中精氨酸与赖氨酸的比例,以检查碱性残基对于抗分枝杆菌活性的重要性。氨基酸的改变降低了抗 E的活性。大肠杆菌比抗耻垢分枝杆菌更大。在颗粒溶素中,环结构中的精氨酸对于抗分枝杆菌活性不是至关重要的,但对细胞毒性却很重要。我们建议相关蛋白颗粒溶素,NK溶素和鸡NK溶素的抗菌域已经保守了它们的3-D结构和它们对分枝杆菌的功能。

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