固有无序蛋白与蛋白质相互作用位点残基特征分析

本文对固有无序蛋白(IDPs)与其他蛋白质相互作用位点残基特征进行了研究.首先在数据库中选出满足条件的109条IDPs蛋白质链及与其他配体蛋白形成的299个IDPs-蛋白质复合物,然后提取复合物中作为相互作用位点的IDPs-蛋白质残基.这109条IDPs链中共含有50 031个氨基酸残基,其中处于作用位点的残基有4 822个.通过分析发现,20种氨基酸在形成IDPs-蛋白质相互作用位点残基时具有不同的倾向性,根据形成作用位点残基的倾向性,20种氨基酸可分成三大类:倾向型氨基酸(ILE、LEU、ARG、PHE、TYR、MET、TRP)、中间型氨基酸(GLN、GLU、THR、LYS、VAL、ASP、HIS)、非倾向型氨基酸(PRO、SER、GLY、ALA、ASN、CYS).研究结果还进一步表明,不同氨基酸在有序区域与无序区域形成IDPs-蛋白质作用位点残基的倾向性不同.其中,氨基酸TRP、LEU、ILE、CYS在有序和无序区域形成作用位点残基的差异性尤为明显,而氨基酸GLU、PHE、HIS、ALA则基本没有多大差别.对IDPs-蛋白质相互作用位点残基理化特征进行分析发现:疏水性强、侧链净电荷量较少、极性较小、溶剂可及性表面积较大、侧链体积较大、极化率较大的氨基酸比较倾向于形成作用位点残基.主成分分析结果显示,残基的极化率、侧链体积和溶剂可及表面积对作用位点残基影响最大.

An Investigation on Characteristic of Residues Involved in Intrinsically Disordered Protein-Protein Interaction

In this study, we investigated the characters of residues in IDPs that involved in the interations with other proteins. Firstly, 109 IDPs' chains and 299 IDPs-protein compounds which meet the requirement in database were selected; secondly, 4 822 interface amino acid residues which involving in interaction were extracted from the totally 50 031 amino acid residues in the 109 IDPs chains. The results indicated that the 20 amino acids have different propensities when forming IDPs-protein's interfaces. Therefore, we divided the 20 amino acids into three parts based on their propensities: propensity amino acids (ILE, LEU, ARG, PHE, TYR, MET, TRP), middle amino acids (GLN, GLU, THR, LYS, VAL, ASP, HIS) and non-propensity amino acids(PRO, SER, GLY, ALA, ASN, CYS). Moreover, the results show that the 20 amino acids have different propensities in IDPs' different regions (ordered or disordered regions). For example, TRP, LEU, ILE and CYS are more frequently observed compared with ordered and disordered regions. However, there are no obvious difference for GLU, PHE, HIS and ALA residues between ordered regions and disordered regions. Besides, the amino acids which have larger hydrophobicity, polarizability, side chain's volume, solvent accessible surface area, smaller polarity and net charge index of side chain tend to be IDPs-Protein's interface. The results obtained by principal components analysis showed that the polarizability, side chain's volume and solvent accessible surface area of residues had more affect on the IDPs-Protein's interaction residues.