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化学学报
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化学学报 ›› 2012, Vol. 70 ›› Issue (03): 318-324.DOI: 10.6023/A1106042 上一篇    下一篇

研究论文

基于VHSE 结构表征的蛋白酶体酶切位点预测及酶切特异性研究

谢江安a, 梅虎a,b, 吕娟a, 潘显超a, 王青a, 张亚兰a   

  1. a 生物流变科学与技术教育部重点实验室 重庆大学 重庆 400044;
    b 重庆大学生物工程学院 重庆 400044
  • 投稿日期:2011-06-04 修回日期:2011-09-04 发布日期:2011-10-26
  • 通讯作者: 梅虎 E-mail:meihu@cqu.edu.cn
  • 基金资助:

    重庆市自然科学基金重点项目(CSTC, 2009BA5068)和重庆大学中央高校基本科研业务费科研专项(CDJXS, 11231177)资助项目.

Studies on the Prediction of Selective Cleavage Sites and Cleavage Profile of Proteasome Using VHSE Amino Acid Descriptor

Xie Jiangana, Mei Hua,b, Lü Juanba, Pan Xianchaoa, Wang Qinga, Zhang Yalana   

  1. a Key Laboratory of Biorheological Science and Technology Ministry of Education, Chongqing University, Chongqing 400044;
    b College of Bioengineering, Chongqing University, Chongqing 400044
  • Received:2011-06-04 Revised:2011-09-04 Published:2011-10-26
  • Supported by:

    Project supported by Chongqing Key Natural Science Foundation (No. 2009BA5068), and the Fundamental Research Funds for the Central Universities (No. 11231177).

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1548

被引次数

7

泛素-蛋白酶体在真核生物的抗原呈递、细胞周期调控和转录因子激活等生理过程中发挥着极为重要的作用, 其核心就是蛋白酶体对底物的选择性酶切作用, 因此对选择性酶切位点的预测一直是计算生物学的一个重点研究内容.针对现有酶切位点预测方法的非线性和物理意义不明确等问题, 借鉴定量构效关系研究方法, 采用基于氨基酸物理化学性质的描述子——VHSE (Principal component score vector of hydrophobic, steric, and electronic properties)对收集的2650 个MHC-I 配体的源蛋白序列进行了结构表征, 在此基础上利用支持向量机建立了蛋白酶体酶切位点的预测模型,其最优线性模型的灵敏度(Sensitivity)、特异性(Specificity)、接受者操作特征曲线下面积(area under receiver operatingcharacteristics curve, AUC)和马休斯相关系数(Matthews coefficient of correlation, MCC)分别为90.18%, 69.63%, 0.8797 和0.6131. 模型分析结果表明: 影响酶切位点选择性的氨基酸性质由大到小依次为: 疏水性、电性和立体特征; P9, P8, P4,P1, P3', P4'和P5'位氨基酸对酶切位点的选择有重要影响, 研究亦显示酶切位点上游P1 位和下游P1'～P5'的“疏水势差”有利于蛋白酶体的切割作用.

关键词: 蛋白酶体, MHC-I 配体, VHSE, 支持向量机, 酶切位点

The ubiquitin-proteasome system (UPS) plays a critical role in proteolysis and degradation in many physiological processes of the eukaryotes, such as antigen presentation, cell cycle regulation, and transcription factors activation. Recently, due to the importance of selective substrate cleavage of proteasome in the UPS, the cleavage site prediction has attracted considerable interest in computational biology. However, the existing methods are mostly based on nonlinear models with little physicochemical meanings. In this paper, VHSE (Principal component score vector of hydrophobic, steric, and electronic properties), a novel set of amino acid descriptors, was used to characterize the source proteins of 2650 natural MHC class I ligands. Based on the structural descriptions of the amino acids adjacent to the cleavage site, support vector machine (SVM) was then employed to establish the prediction models using linear and RBF kernel functions. A linear SVM model with high prediction capability was obtained, of which the sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and the Matthews correlation coefficient (MCC) were 0.9018, 0.6963, 0.8797 and 0.6131, respectively. The results showed that the hydrophobic, electronic, and steric properties of the amino acids adjacent to the cleavage site are closely related to the selective substrate cleavage, especially for those at the positions of P9, P8, P4, P1, P3', P4', and P5'. The results also showed that hydrophobic potential difference between P1 position and P1'～P5' positions may benefit the cleavage process of the proteasome.

Key words: proteasome, MHC-I ligand, VHSE, SVM, cleavage site