Characterization of domain-peptide interaction interface: prediction of SH3 domain-mediated protein-protein interaction network in yeast by generic structure-based models.
Characterization of domain-peptide interaction interface: prediction of SH3 domain-mediated protein-protein interaction network in yeast by generic structure-based models.
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DOI：
10.1021/pr3000688
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发表时间：
2012-05-04
影响因子：
4.4
通讯作者：
Wang W
中科院分区：
文献类型：
--
作者：
Hou T;Li N;Li Y;Wang W
SH 3结构域是肽识别模块（PRM），测定其结合特异性对于了解其生物学功能和重建SH 3介导的蛋白质-蛋白质相互作用网络具有重要意义。在本研究中，SH 3-肽相互作用的I类和II类SH 3结构域的特征在于分子间的残基-残基相互作用网络。我们开发了通用MIEC-SVM模型来推断SH 3结构域肽识别特异性，达到了令人满意的预测精度。通过在残基水平上研究结构域-肽的识别机制，我们发现I类和II类结合肽虽然占据SH 3的相同结合位点，但具有不同的结合模式。此外，我们预测了SH 3结构域在酵母蛋白质组中的潜在结合伴侣，并构建了SH 3介导的蛋白质-蛋白质相互作用网络。与实验确定的相互作用的比较证实了我们的方法的有效性。这项研究表明，我们复杂的计算方法不仅提供了一个强大的平台，破译蛋白质识别代码在分子水平上，但也允许识别肽介导的蛋白质相互作用在蛋白质组学规模。我们相信，这种方法一般适用于其他结构域-肽相互作用。
Determination of the binding specificity of SH3 domain, a peptide recognition module (PRM), is important to understand their biological functions and reconstruct the SH3-mediated protein–protein interaction network. In the present study, the SH3-peptide interactions for both class I and II SH3 domains were characterized by the intermolecular residue–residue interaction network. We developed generic MIEC-SVM models to infer SH3 domain-peptide recognition specificity that achieved satisfactory prediction accuracy. By investigating the domain–peptide recognition mechanisms at the residue level, we found that the class-I and class-II binding peptides have different binding modes even though they occupy the same binding site of SH3. Furthermore, we predicted the potential binding partners of SH3 domains in the yeast proteome and constructed the SH3-mediated protein–protein interaction network. Comparison with the experimentally determined interactions confirmed the effectiveness of our approach. This study showed that our sophisticated computational approach not only provides a powerful platform to decipher protein recognition code at the molecular level but also allows identification of peptide-mediated protein interactions at a proteomic scale. We believe that such an approach is general to be applicable to other domain–peptide interactions.