肺癌组织中SOX4突变蛋白三级结构的建模及分析(英文)

Modeling and analysis the tertiary structures of the SOX4 mutants encoded proteins of lung cancer tissues

SOX家族与很多人类肿瘤的发生有关.对人类肺癌组织中的SOX4进行测序,发现该基因HMG-box区有突变发生并导致SOX4蛋白的107密码子发生突变.以三级结构已知的SOX2为模板,采用同源建模方法对突变和正常SOX4蛋白FMG-box进行建模.结果显示突变和正常SOX4蛋白的三级结构很相似,且突变导致107密码子位置的侧链结构不稳定.提示该位置的不稳定可能会影响突变SOX4蛋白侧链的弹性,并有可能影响相应蛋白的功能.表面静电分析显示SOX4蛋白C端有一个可能与其它小分子或蛋白质的相互作用位点的N/C腔.这些结果显示SOX4蛋白的上述空间结构可能与其活性与功能的调控有关,而SOX4突变可能与肺癌的发生和转移有关.

SOX family has been associated with a variety of human tumors. The SOX4-gene HMG-box of lung cancer tissues was sequenced and identified mutation sites, and cause the codon 107 of SOX4 protein was mutant. The tertiary structures of mutant and normal SOX4 proteins were modeled using homology modeling method, and the known tertiary structure of SOX2 as template. The results showed that the tertiary structures of the mutant and normal SOX4 is similar, and the side-chain conformations of the codon 107 region were relatively unstable. It suggested that the instability of codon 107 might affect the flexibility of the side chains of mutant SOX4 and could affect the functions of the corresponding protein. Analysis of the Electrostatic Surfaces showed the C-terminal half of SOX4 form an N/C cavity where interactions with organic molecules or proteins could be possible. These results indicated that the spatial structure of SOX4 more likely to regulate the activity and function of this protein, and mutations in the SOX4 gene were likely to be associated with lung carcinogenesis and metastasis.