Hydration of protein–RNA recognition sites

Abstract

We investigate the role of water molecules in 89 protein–RNA complexes taken from the Protein Data Bank. Those with tRNA and single-stranded RNA are less hydrated than with duplex or ribosomal proteins. Protein–RNA interfaces are hydrated less than protein–DNA interfaces, but more than protein–protein interfaces. Majority of the waters at protein–RNA interfaces makes multiple H-bonds; however, a fraction do not make any. Those making H-bonds have preferences for the polar groups of RNA than its partner protein. The spatial distribution of waters makes interfaces with ribosomal proteins and single-stranded RNA relatively ‘dry’ than interfaces with tRNA and duplex RNA. In contrast to protein–DNA interfaces, mainly due to the presence of the 2′OH, the ribose in protein–RNA interfaces is hydrated more than the phosphate or the bases. The minor groove in protein–RNA interfaces is hydrated more than the major groove, while in protein–DNA interfaces it is reverse. The strands make the highest number of water-mediated H-bonds per unit interface area followed by the helices and the non-regular structures. The preserved waters at protein–RNA interfaces make higher number of H-bonds than the other waters. Preserved waters contribute toward the affinity in protein–RNA recognition and should be carefully treated while engineering protein–RNA interfaces.

How Ligand Binding Affects the Dynamical Transition Temperature in Proteins

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“…[18][19][20] In recent years, much attention has been paid to examining the general interface properties of protein-RNA complexes. [21][22][23][24][25][26][27][28] Bahadur et al 22 analyzed PRIs in terms of interface size, composition, polar interactions and atomic packing and found electrostatic complementation, base recognition and shape complementarity on the interfaces of PRIs. By investigating the preferred RNA structural states in protein-binding regions, Gupta et al 24 observed strong preferences for both RNA bases and RNA structural states in protein-RNA interactions, indicating their mutual importance in protein recognition.…”

Structure alignment-based classification of RNA-binding pockets reveals regional RNA recognition motifs on protein surfaces

“…Revealing the RNA-binding structure motifs will provide insightful clues for deciphering the mechanisms of protein-RNA interactions and provide valuable knowledge for protein engineering, such as drug target design for silencing specific RNAs after transcription [3, 4]. Moreover, numerous diseases have been found to be related to dysfunctions of protein-RNA interactions due to RNA-mediated post-transcriptional gene regulation [5–7].…”