Structure-based analysis of cooperativity in protein-DNA recognition

構造情報に基づく蛋白質・DNA認識における協同性の解析

田中 昭宏*; 藤井 聡*; 河野 秀俊; 皿井 明倫*

Tanaka, Akihiro*; Fujii, Satoshi*; Kono, Hidetoshi; Sarai, Akinori*

Gene regulation is achieved by a complex combination of transcription factors and their targets. This is highly cooperative nonlinear system, in which minute changes in input signal are amplified to produce highly visible outcome. Thus, it is crucial to understand the role of cooperativity in gene regulation. Here, we focus on the structural aspect of cooperativity at the protein-DNA recognition level. We have used a knowledge-based approach, utilizing structural data of protein-DNA complexes, to derive empirical potential for the specific interactions between bases and amino acids. Then, these potentials were used to quantify the specificity of protein-DNA recognition. In this study, we apply this method to examine the effects of binding cooperativity on the specificity of protein-DNA recognition. For this purpose, we collected structures of protein-DNA complexes, with a protein bound to DNA and the same protein together with its partner bound to DNA. By computing the specificity for these homo- and hetero-complexes, we can examine if the cooperative binding enhance the specificity in a systematic manner. We also examined the conformation changes of proteins and DNAs between the homo- and hetero-complexes, to find any relationship between structure and specificity in the cooperative recognition. We show by several examples that the protein-DNA recognition is indeed cooperative and the specificity is enhanced by structural changes during the recognition.