卵巢癌诊断新基因HELQ的生物信息学分析

Bioinformatics analysis of a new diagnostic marker of ovarian cancer HELQ

目的本研究拟采用生物信息学工具分析卵巢癌易感基因HELQ所编码蛋白的结构及结构与功能的关系,并初步探讨其对肿瘤发生的影响。方法采用Ex PASy服务器中的工具分析HELQ蛋白的理化特征;分别采用PSORTⅡ和TMHMM预测HELQ蛋白的亚细胞定位和跨膜拓扑结构;采用Signal P 4.0预测HELQ的信号肽;采用Scan Prosite和SMART分析HELQ的功能结构域以及结构域分区,采用PSIPRED和I-TASSER预测HELQ蛋白的二级和三级结构以及配体结合位点;最后采用STRING 10.0预测HELQ与其他蛋白质的交互作用。结果 HELQ主要定位在细胞核(47.8%)和细胞质(39.1%)中,有4个保守结构域DEXDc、HELICc、HHH_5和PRK02362,并包含解旋酶ATP结合区和解旋酶C端结合区两个功能结构域;成功建立了HELQ的二级和三级结构模型,其中二级结构中α螺旋、无规则卷曲及折叠结构比例分别为54.0%、31.0%和6.0%。三维配体结构分析结果可见,HELQ包含一个酶活性中心位点His341,催化Ile333、Lys335、Tyr337、Gln340、Pro360、Thr361、Ser362、Gly363、Gly364、Lys365、Thr366、Leu367、Glu464和Ala711等结合位点与配体ATP结合。交联蛋白质分析发现HELQ可能与RAD51、POLA1、PLON、FANCD2、DHX8等蛋白存在交互作用。结论 HELQ具有ATP依赖性解旋酶活性,参与DNA损伤的修复过程,可能是其低表达时引起卵巢癌等恶性肿瘤发生的机制。

Objective To analyze the structure of protein encoded by ovarian cancer susceptibility gene HELQ and relationship between the structure and function by using bioinformatics tools and to discuss its effect on occurrence of tumors. Methods Tools of Ex PASy Server were employed to analyze the physicochemical properties of HELQ protein. Its subcellular localization and transmembrane topology were predicted by PSORTⅡand TMHMM,respectively. Signal peptide of HELQ was predicted by Signal P 4. 0. Scan Prosite and SMART were used to analyze function domain and domain partition of HELQ. PSIPRED and I-TASSER were employed to predict secondary structure and three-dimensional model and find ligandbinding sites of HELQ protein. And STRING 10. 0 was used to predict the interaction of HELQ with other proteins. Results HELQ protein was mainly located in nucleus（ 47. 8%） and cytoplasm（ 39. 1%）. HELQ had 4 conserved domains,consisting of DEXDc,HELICc,HHH_5 and PRK02362,and contained 2 function domains,helicase_ATP binding and helicase_C terminal binding. Secondary structure and three-dimensional model were constructed. In secondary structure,proportion of α helix,random coils and β-structure was 54. 0%,31. 0% and 6. 0%,respectively. Results of three-dimensional model analysis found that HELQ had an enzyme activity site His341,catalyzing binding of binding sites appeared in Ile333,Lys335,Tyr337,Gln340,Pro360,Thr361,Ser362,Gly363,Gly364,Lys365,Thr366,Leu367,Glu464 and Ala711 and ligand ATP. Result of cross-linked protein analysis discovered that HELQ might have interaction with RAD51,POLA1,PLON,FANCD2 and DHX8. Conclusion HELQ possesses ATP dependent helicase activity and participate in DNA repair process. Its low expression is possible pathogenic mechanism of ovarian cancer or other malignant tumor.