正常及突变角蛋白K1部分螺旋亚区分子模拟及其比较

Comparison of two molecular models between normal and mutated segment coil domain of keratin 1

目的研究先天性大疱性鱼鳞病样红皮病(BCIE)患者存在角蛋白K1E477K突变的可能致病途径。方法对K1E477K突变所在的K12B尾区进行分子模拟,观察角蛋白中氨基酸之间的相互作用,以及突变所造成的影响。结果突变后的赖氨酸与对应链上的精氨酸理论距离增大。结论突变使分子间相互作用减弱,影响了角蛋白K1/K10异源二聚体的稳定性,这可能是导致角蛋白细丝网络破坏的部分原因。

Objective: To find the possible role of the K1 E477K gene mutation in bullous congenital ichthyosiform erythroderma (BCIE). Methods: Computer models of K1 2B domain were generated to visualize the interaction between amino acids of keratins and the changes caused by the substitution. Results: Molecular modeling showed that the mutation led to the increased distance between a lysine and its corresponding arginine in the other chain. Conclusions: The mutated keratin can weaken intermolecular joints and decrease the stability of hererodimer, which disrupt the keratin intermediate filaments network.