A structural dissection of protein-RNA interactions based on different RNA base areas of interfaces

Abstract

Protein-RNA interactions are very common cellular processes, but the mechanisms of interactions are not fully understood, mainly due to the complicated RNA structures. By the elaborate investigation on RNA structures of protein-RNA complexes, it was firstly found in this paper that RNAs in these complexes could be clearly classified into three classes (high, medium and low) based on the different levels of P _base (the percentage of base area buried in the RNA interface). In view of the three RNA classes, more detailed analyses on protein-RNA interactions were comprehensively performed from various aspects, including interface area, structure, composition and interaction force, so as to achieve a deeper understanding of the recognition specificity for the three classes of protein-RNA interactions. According to our classification strategy, the three complex classes have significant differences in terms of almost all properties. Complexes in the high class have short and extended RNA structures and behave like protein-ssDNA interactions. Their hydrogen bonds and hydrophobic interactions are strong. For complexes in low class, their RNA structures are mainly double-stranded, like protein-dsDNA interactions, and electrostatic interactions frequently occur. The complexes in medium class have the longest RNA chains and largest average interface area. Meanwhile, they do not show any preference for the interaction force. On average, in terms of composition, secondary structures and intermolecular physicochemical properties, significant feature preferences can be observed in high and low complexes, but no highly specific features are found for medium complexes. We found that our proposed P _base is an important parameter which can be used as a new determinant to distinguish protein-RNA complexes. For high and low complexes, we can more easily understand the specificity of the recognition process from the interface features than for medium complexes. In the future, medium complexes should be our research focus to further structurally analyze from more feature aspects. Overall, this study may contribute to further understanding of the mechanism of protein-RNA interactions on a more detailed level.

Fig. 1. Violin plot combining the box plot and density trace for P_ribose, P_phosphate and P_base in the initial dataset.

Fig. 2. Distribution of P_ribose, P_phosphate and P_base in 137 non-redundant protein–RNA complexes. (A) The percentage of P_ribose, P_phosphate and P_base in different types of protein–RNA complexes. (B) The box plot for P_base in each class.

Fig. 3. Bubble chart of R_pair in the three classes. The bigger bubble and the deeper color indicate higher frequency of R_pair in each class.

Fig. 4. Size of the interfaces and interface area ratio of our dataset. (A) The frequency histogram of interface area size. (B) The box plot for interface area ratio of the three classes.

Fig. 5. Analysis of the correlation coefficients between N_atoms (or N_residues/N_nucleotides) and interface area. (A) Number of interface atoms against the interface area for the three classes. (B) Interface residues or nucleotides against the interface area for the three classes.

Fig. 6. Amino acid composition and propensity of each class. (A) The average percentage of 20 amino acids in the interface of each class. (B) The average propensity of 20 amino acids in each class.

Fig. 7. Protein secondary structure composition and propensity of each class. (A) The average percentage of secondary structures in the interface of each class. (B) The average propensity of secondary structures in each class.

Fig. 8. The distribution of the overlapped percentage between the largest electrostatic positive patches and interface.

Fig. 9. Pie chart of the distribution of the five categories of P̄_h (the percent overlap between hydrophobic interface and RNA-binding interfaces) in each class. The first to the fifth categories are designated as the P̄_h ranges of 0–20%, 20–40%, 40–60%, 60–80% and 80–100%, respectively, as indicated by dark blue, red, green, dark purple and cyan, respectively.