首页> 外文期刊>African Journal of Biotechnology >Structural analysis of deafness associated E216V mutation in human myosin VI protein
【24h】

Structural analysis of deafness associated E216V mutation in human myosin VI protein

机译:人肌球蛋白VI蛋白中与耳聋相关的E216V突变的结构分析

获取原文
           

摘要

Deafness is the most?common form of sensory impairment in humans.?Several mutations have been reported in the myosin VI proteins that are responsible for autosomal dominant and recessive deafness. One such missense mutation is that which changes glutamate (E) to valine (V) at amino acid 216 (E216V). The mutation resides in the myosin VI head domain; however, detailed insights regarding the impact of this mutation on structural stability are not known. To characterize the potential impact of this mutation on protein stability and its association with deafness, we performed computational sequence and structural analysis of normal and mutated myosin VI.?Overall, protein stability declined when the mutation was introduced, as predicted by I-mutant and Cologne University Protein Stability Analysis Tool (CUPSAT). Similarly, a decline in hydrophobicity around position 216 was observed.Phosphorylation of myosin VI was also observed to be influenced by the E216V mutation. Furthermore, a three-dimensional structure of myosin VI was studied using Swiss-PdbViewer to identify structural variations in the protein that may occur as a result of the E216V mutation. Distortion in the?hydrogen bonding between Val216 and Ser449 in the mutated protein structure was observed, exposing the Ser449 hydroxyl group and reducing overall protein stability.
机译:耳聋是人类最常见的感觉障碍形式。在肌球蛋白VI蛋白中已报道了几种突变,这些突变导致常染色体显性和隐性耳聋。一种这样的错义突变是在氨基酸216(E216V)处将谷氨酸(E)改变为缬氨酸(V)的突变。该突变位于肌球蛋白VI的头部结构域。但是,有关此突变对结构稳定性的影响的详细见解尚不清楚。为了表征该突变对蛋白质稳定性及其与耳聋的关系的潜在影响,我们对正常和突变的肌球蛋白VI进行了计算序列和结构分析。总的来说,引入突变后蛋白质稳定性下降了,正如I-mutant和科隆大学蛋白质稳定性分析工具(CUPSAT)。同样,在216位附近观察到疏水性下降。还观察到肌球蛋白VI的磷酸化受到E216V突变的影响。此外,使用Swiss-PdbViewer对肌球蛋白VI的三维结构进行了研究,以鉴定可能由于E216V突变而导致的蛋白质结构变化。观察到突变的蛋白质结构中Val216和Ser449之间的氢键扭曲,暴露了Ser449羟基并降低了整体蛋白质稳定性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号