Exploring the Nature of Hydrogen Bonding between RNA and Proteins: A Comprehensive Analysis of RNA : Protein Complexes.

A nonredundant dataset of ∼300 high (up to 2.5 Å) resolution X-ray structures of RNA:protein complexes were analyzed for hydrogen bonds between amino-acid residues and canonical ribonucleotides (rNs). The identified 17100 contacts were classified based on the identity (rA, rC, rG or rU) and interacting fragment (base, sugar, or ribose) of the rN, the nature (polar or nonpolar) and interacting moiety (main chain or side chain) of the amino-acid residue, as well as the rN and amino-acid atoms participating in the hydrogen bonding. 80 possible hydrogen-bonding combinations (4 (rNs) X 20 (amino acids)) involve a wide variety of RNA and protein types and are present in multiple occurrences in almost all PDB files. Comparison with the analogously-selected DNA:protein complexes reveals that the absence of 2'-OH group in DNA mainly accounts for the differences in DNA:protein and RNA:protein hydrogen bonding. Search for intrinsically-stable base:amino acid pairs containing single or multiple hydrogen bonds reveals 37 unique pairs, which may act as well-defined RNA:protein interaction motifs. Overall, our work collectively analyzes the largest set of nucleic acid-protein hydrogen bonds to date, and therefore highlights several trends that may help frame structural rules governing the physiochemical characteristics of RNA:protein recognition.