Structure-based bioinformatics analyses and a prediction method of protein-RNA interfaces

蛋白質とRNAの相互作用の構造バイオインフォマティクス解析と予測

Kim, O. T. P.*; 由良 敬; 郷 信広

Kim, O. T. P.*; Yura, Kei; Go, Nobuhiro

蛋白質とRNAとの相互作用は、生体中の多くの局面で見られる。転写翻訳などにおいてどのような相互作用がその機能を実現しているのかを知るためには、蛋白質とRNAの相互作用を原子解像度で知る必要があるが、まだまだ情報がそろっていない。そこで、われわれは、RNAに結合する蛋白質の立体構造が判明したときに、どこがRNAとの相互作用面であるかを推定するバイオインフォマティクスの手法を新規に考案する。この方法を用いると高い精度でRNA結合面を推定することができる。本手法をRNA輸送システムに適用した。

Protein-RNA interactions play essential roles in a number of regulatory mechanisms of gene expression such as RNA splicing, transport and translation. Bioinformatics approach has been effective and rewarding in studying protein-nucleic acid interactions, especially protein-DNA. As the number of available protein-RNA complexes has increased, it is now possible to statistically examine protein-RNA interactions based on 3D structures. We carried out computational analyses of 86 non-homologous protein-RNA complexes retrieved fromP rotein Data Bank. Interface residue propensities, which give a measure forthe relative importance of different amino acid residues in the RNA-binding site, were calculated for both a single residue (singlet) and a residue pair(doublet). The result of singlet residue propensity showed that Arg, Lys, His, Phe, Tyr, Met and Gly were favored in RNA-binding site. The residue doublet interface propensity denoted the significant additional information compared with the sum of singlet propensities of the residues at protein-RNA interface. The interface residue propensities were used as parameters to predict protein-RNA interface. The accuracy of the prediction method was tested byjack-knife method, which attained more than 60% on average. The prediction method was applied to RNA-binding proteins with known 3D structures: mRNA export factors TAP, Mex67 and Mtr2. The prediction enables us to point out the candidate interfaces, which are consistent with previous studies and can betested by mutation experiments leading to elucidation of protein-RNA complexes.