Anatomy Of Noncovalent Interactions Between The Nucleobases Or Ribose And Pi-Containing Amino Acids In Rna-Protein Complexes

A set of >300 nonredundant high-resolution RNA-protein complexes were rigorously searched for pi-contacts between an amino acid side chain (W, H, F, Y, R, E and D) and an RNA nucleobase (denoted pi-pi interaction) or ribose moiety (denoted sugar-pi). The resulting dataset of >1500 RNA-protein pi-contacts were visually inspected and classified based on the interaction type, and amino acids and RNA components involved. More than 80% of structures searched contained at least one RNA-protein pi-interaction, with pi-pi contacts making up 59% of the identified interactions. RNA-protein pi-pi and sugar-pi contacts exhibit a range in the RNA and protein components involved, relative monomer orientations and quantum mechanically predicted binding energies. Interestingly, pi-pi and sugar-pi interactions occur more frequently with RNA (4.8 contacts/structure) than DNA (2.6). Moreover, the maximum stability is greater for RNA-protein contacts than DNA-protein interactions. In addition to highlighting distinct differences between RNA and DNA-protein binding, this work has generated the largest dataset of RNA-protein pi-interactions to date, thereby underscoring that RNA-protein pi-contacts are ubiquitous in nature, and key to the stability and function of RNA-protein complexes.