Small Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA

TitleSmall Details Matter: The 2′-Hydroxyl as a Conformational Switch in RNA
Publication TypeJournal Article
Year of Publication2016
AuthorsDarré, Leonardo, Ivani Ivan, Dans Pablo D., Gómez Hansel, Hospital Adam, and Orozco Modesto
JournalJournal of the American Chemical Society
Volume138
Issue50
Pagination16355 - 16363
Date Published12/2016
ISBN Number0002-7863
Abstract

While DNA is mostly a primary carrier of genetic information and displays a regular duplex structure, RNA can form very complicated and conserved 3D structures displaying a large variety of functions, such as being an intermediary carrier of the genetic information, translating such information into the protein machinery of the cell, or even acting as a chemical catalyst. At the base of such functional diversity is the subtle balance between different backbone, nucleobase, and ribose conformations, finely regulated by the combination of hydrogen bonds and stacking interactions. Although an apparently simple chemical modification, the presence of the 2′OH in RNA has a profound effect in the ribonucleotide conformational balance, adding an extra layer of complexity to the interactions network in RNA. In the present work, we have combined database analysis with extensive molecular dynamics, quantum mechanics, and hybrid QM/MM simulations to provide direct evidence on the dramatic impact of the 2′OH conformation on sugar puckering. Calculations provide evidence that proteins can modulate the 2′OH conformation to drive sugar repuckering, leading then to the formation of bioactive conformations. In summary, the 2′OH group seems to be a primary molecular switch contributing to specific protein–RNA recognition.While DNA is mostly a primary carrier of genetic information and displays a regular duplex structure, RNA can form very complicated and conserved 3D structures displaying a large variety of functions, such as being an intermediary carrier of the genetic information, translating such information into the protein machinery of the cell, or even acting as a chemical catalyst. At the base of such functional diversity is the subtle balance between different backbone, nucleobase, and ribose conformations, finely regulated by the combination of hydrogen bonds and stacking interactions. Although an apparently simple chemical modification, the presence of the 2′OH in RNA has a profound effect in the ribonucleotide conformational balance, adding an extra layer of complexity to the interactions network in RNA. In the present work, we have combined database analysis with extensive molecular dynamics, quantum mechanics, and hybrid QM/MM simulations to provide direct evidence on the dramatic impact of the 2′OH conformation on sugar puckering. Calculations provide evidence that proteins can modulate the 2′OH conformation to drive sugar repuckering, leading then to the formation of bioactive conformations. In summary, the 2′OH group seems to be a primary molecular switch contributing to specific protein–RNA recognition.

URLhttp://dx.doi.org/10.1021/jacs.6b09471
Short TitleJ. Am. Chem. Soc.
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