National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan.
Proteins. 2012 Oct;80(10):2426-36. doi: 10.1002/prot.24127. Epub 2012 Jul 10.
Proteins interact with different partners to perform different functions and it is important to elucidate the determinants of partner specificity in protein complex formation. Although methods for detecting specificity determining positions have been developed previously, direct experimental evidence for these amino acid residues is scarce, and the lack of information has prevented further computational studies. In this article, we constructed a dataset that is likely to exhibit specificity in protein complex formation, based on available crystal structures and several intuitive ideas about interaction profiles and functional subclasses. We then defined a "structure-based specificity determining position (sbSDP)" as a set of equivalent residues in a protein family showing a large variation in their interaction energy with different partners. We investigated sequence and structural features of sbSDPs and demonstrated that their amino acid propensities significantly differed from those of other interacting residues and that the importance of many of these residues for determining specificity had been verified experimentally.
蛋白质与不同的伴侣相互作用以执行不同的功能，阐明蛋白质复合物形成中伴侣特异性的决定因素非常重要。尽管以前已经开发出用于检测特异性决定位置的方法，但这些氨基酸残基的直接实验证据很少，并且缺乏信息也阻止了进一步的计算研究。在本文中，我们根据现有晶体结构和关于相互作用模式和功能子类的几个直观想法，构建了一个可能在蛋白质复合物形成中表现出特异性的数据集。然后，我们将“基于结构的特异性决定位置（sbSDP）”定义为在蛋白质家族中一组等效残基，它们与不同伴侣的相互作用能有很大差异。我们研究了 sbSDP 的序列和结构特征，并证明它们的氨基酸倾向性与其他相互作用残基明显不同，并且许多这些残基对于确定特异性的重要性已通过实验验证。
