卵巢癌HELQ蛋白结构和功能的生物信息学工具分析预测

摘要

目的 预测卵巢癌抑癌基因HELQ编码蛋白(HELQ蛋白)的结构和功能.方法 采用ExPASy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SignalP 4.0预测HELQ蛋白的信号肽.采用ScanProsite和SMART分析HELQ蛋白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.采用STRING 10.0预测HELQ蛋白与其他蛋白的交互作用.结果 HELQ蛋白主要定位在细胞核(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蛋白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%、31%和6%.三维配体结构分析发现HELQ蛋白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蛋白可能与RAD51、POLA1、PLON、FANCD2、DHX8等蛋白存在交互作用.结论 HELQ蛋白可能具有ATP依赖性解旋酶的结构和功能,参与DNA损伤的修复过程.%Objective To predict the structure and function of ovarian cancer anti-tumor gene HELQ protein. Meth-ods The tools of ExPASy Server were employed to analyze the physicochemical properties of HELQ protein. Its subcellu-lar localization and transmembrane topology were predicted by PSORTⅡand TMHMM,respectively. The signal peptide of HELQ was predicted by SignalP 4. 0. ScanProsite and NCBI conserved domain search data were used to analyze the function domain and conserved domain. PSIPRED and I-TASSER were employed to construct the secondary structure and three-di-mensional model and find the ligand binding sites of HELQ. STRING 10. 0 was used to predict the interaction of HELQ with other proteins. Results The HELQ protein was mainly located in the nucleus (47. 8%)and cytoplasm (39. 1%). HELQ had 4 conserved domains,consisting of DEAD,HELICc,HHH_5,and PRK02362,and contained 2 function do-mains:Helicase_ATP-Bind_1 and Helicase_Cter. The secondary structure and three-dimensional model were constructed. In the secondary structure,HELQ was composed of α helix (54%),random coils (31%),and 10. 26% β-structure. The results of three-dimensional model found that HELQ had a enzyme activity site His341 and the ligand binding sites appeared in Ile333,Lys335,Tyr337,Gln340,Pro360,Thr361,Ser362,Gly363,Gly364,Lys365,Thr366,Leu367,Glu464 and Ala711 which combined with ATP. The result of cross-linked protein analysis discovered that HELQ might be interaction with RAD51,POLA1,PLON,FANCD2,and DHX8. Conclusion HELQ protein may have ATP-dependent helicase structure and function,and participate in the DNA damage repair process.