Hydration of protein-RNA recognition sites.
Bottom Line: Majority of the waters at protein-RNA interfaces makes multiple H-bonds; however, a fraction do not make any.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.
Affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.Show MeSH
Related in: MedlinePlus
Mentions: Bridging waters must make at least one H-bond with both the interacting partners. Since water has two donors and two acceptors, tetrahedrally oriented, just two H-bonds will not be specific because the water can potentially rotate to present either a donor or acceptor to the base (27). Therefore, specificity only arises when the water makes more than two H-bonds simultaneously. Figure 2 shows the frequency distribution of interface waters making up to four H-bonds. About 60% of them make one or two H-bonds with the protein polar groups. This percentage increases to 67% with the RNA polar groups. These waters are involved in non-specific recognition, mostly filling up the interface cavities. They also contribute toward maximizing the surface complementarity at the interface (26). Besides, only 6% of the interface waters make three or four H-bonds with the protein polar groups. This percentage increases to 13% with the RNA polar groups. They largely contribute to the specificity in the recognition process, which is exemplified in the interface of arginyl-tRNA synthetase and its cognate tRNA (Arg) (PDB id: 1F7U) (48). This interface contains 116 waters, and 96 of them make at least one H-bond with an interface atom. Delagoutte et al. (48) hypothesized that the water-mediated interactions confer a high adaptability to the interface while providing the required specificity and affinity. We identified a significant number (20%) of waters making three and four H-bonds at this interface, contributing to the specificity of the recognition. In our dataset, 34% of interface waters do not make any H-bond with the protein polar groups, but they make H-bonds with the RNA polar groups. Counter example also exists, however, with a lower fraction of 20%, indicating that waters at the protein–RNA interfaces have preference to make H-bonds with RNA than its partner protein.
Affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur-721302, India.