Amino acid residue doublet propensity in the protein–RNA interface and its application to RNA interface prediction

Abstract

Protein–RNA interactions play essential roles in a number of regulatory mechanisms for gene expression such as RNA splicing, transport, translation and post-transcriptional control. As the number of available protein–RNA complex 3D structures has increased, it is now possible to statistically examine protein–RNA interactions based on 3D structures. We performed computational analyses of 86 representative protein–RNA complexes retrieved from the Protein Data Bank. Interface residue propensity, a measure of the relative importance of different amino acid residues in the RNA interface, was calculated for each amino acid residue type (residue singlet interface propensity). In addition to the residue singlet propensity, we introduce a new residue-based propensity, which gives a measure of residue pairing preferences in the RNA interface of a protein (residue doublet interface propensity). The residue doublet interface propensity contains much more information than the sum of two singlet propensities alone. The prediction of the RNA interface using the two types of propensities plus a position-specific multiple sequence profile can achieve a specificity of about 80%. The prediction method was then applied to the 3D structure of two mRNA export factors, TAP (Mex67) and UAP56 (Sub2). The prediction enables us to point out candidate RNA interfaces, part of which are consistent with previous experimental studies and may contribute to elucidation of atomic mechanisms of mRNA export.

Structural Prediction of Protein-Rna Interaction by Computational Docking With Propensity-Based Statistical Potentials

“…9,15,16 In practically all of the studies, the favored residues are R and K, but their pairwise preferences for the ribonucleotides change. In our work here and in others, 9,16 there are no significant differences on the preferences of R and K for any ribonucleotide, but in some studies they see preferred pairs as R-U, 11,12,15 or K-A. 11,12 Interestingly, in our study we can see H residues with higher pairwise propensities, while this is not observed in any of the previous studies.…”

“…In our work here and in others, 9,16 there are no significant differences on the preferences of R and K for any ribonucleotide, but in some studies they see preferred pairs as R-U, 11,12,15 or K-A. 11,12 Interestingly, in our study we can see H residues with higher pairwise propensities, while this is not observed in any of the previous studies. Histidine residue can act as positively charged, depending on the environment, so this can explain its high propensities.…”

“…[6][7][8][9][10][11][12][13][14][15][16] Some of these studies reported individual propensities and all-atom statistical potentials for the characterization of modeled protein-RNA interactions at atomic level. For instance, all-atom hydrogen-bond statistical potentials have been applied to identify near-native docking solutions.…”

Human Origin Recognition Complex Binds Preferentially to G-quadruplex-preferable RNA and Single-stranded DNA

“…The partial sequence of human ORC1 from 1 to 530 was submitted to FUGUE server. Once the threedimensional structure was predicted, RNA-binding residues were further predicted using KYG method (21).…”

“…Residues critical for RNA/ssDNA binding within the domain were predicted using the KYG method (21). There are two candidate surfaces for RNA/ssDNA binding, one of which coincides with the S-adenosyl-L-homocysteine (SAH) binding site (Fig.…”