Adenine protonation enables cyclic-di-GMP binding to cyclic-GAMP sensing riboswitches

RNA
Heiko KellerJens Wöhnert

Abstract

In certain structural or functional contexts, RNA structures can contain protonated nucleotides. However, a direct role for stably protonated nucleotides in ligand binding and ligand recognition has not yet been demonstrated unambiguously. Previous X-ray structures of c-GAMP binding riboswitch aptamer domains in complex with their near-cognate ligand c-di-GMP suggest that an adenine of the riboswitch either forms two hydrogen bonds to a G nucleotide of the ligand in the unusual enol tautomeric form or that the adenine in its N1 protonated form binds the G nucleotide of the ligand in its canonical keto tautomeric state. By using NMR spectroscopy we demonstrate that the c-GAMP riboswitches bind c-di-GMP using a stably protonated adenine in the ligand binding pocket. Thereby, we provide novel insights into the putative biological functions of protonated nucleotides in RNA, which in this case influence the ligand selectivity in a riboswitch.

References

May 11, 1990·Biochemistry·J D PuglisiI Tinoco
Jun 6, 1998·Nucleic Acids Research·A S BrodskyJ R Williamson
May 7, 2002·Nature Structural Biology·Anna HupplerSamuel E Butcher
Sep 13, 2002·Journal of Molecular Biology·Paul L NixonDavid P Giedroc
Oct 12, 2002·Science·Peter B RupertAdrian R Ferré-D'Amaré
Oct 3, 2003·Chembiochem : a European Journal of Chemical Biology·Boris FürtigHarald Schwalbe
Apr 6, 2005·Molecular Cell·J Kenneth WickiserDonald M Crothers
Aug 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Peter V CornishDavid P Giedroc
Mar 31, 2009·Analytical Biochemistry·Feng RaoZhao-Xun Liang
Apr 14, 2009·Nature Methods·Daniel G GibsonHamilton O Smith
Nov 10, 2009·Nature Structural & Molecular Biology·Kathryn D SmithScott A Strobel
Nov 10, 2009·Nature Structural & Molecular Biology·Nadia KulshinaAdrian R Ferré-D'Amaré
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Timothy J WilsonDavid M J Lilley
Jul 16, 2010·Angewandte Chemie·Elke Duchardt-FernerJens Wöhnert
Aug 10, 2010·Biochemistry·Kathryn D SmithScott A Strobel
Jul 8, 2011·Accounts of Chemical Research·Jennifer L WilcoxPhilip C Bevilacqua
Nov 29, 2011·Nature·Brian Houck-LoomisVictoria M D'Souza
Mar 23, 2012·Nature·Natalia DemeshkinaGulnara Yusupova
Sep 11, 2012·Journal of the American Chemical Society·Stephanie Kath-SchorrDavid M J Lilley
Feb 26, 2013·Journal of the American Chemical Society·Jennifer L Wilcox, Philip C Bevilacqua
Mar 16, 2013·Journal of the American Chemical Society·Colleen A KellenbergerMing C Hammond
Jun 19, 2013·Proceedings of the National Academy of Sciences of the United States of America·Darian D CashJuli Feigon
Jun 22, 2014·RNA·Sina R Gottstein-SchmidtkeJens Wöhnert
Jul 21, 2014·Nature Chemical Biology·Yijin LiuDavid M J Lilley
Nov 30, 2014·Methods in Enzymology·Pallavi Thaplyal, Philip C Bevilacqua
Mar 13, 2015·Nature·Isaac J KimseyHashim M Al-Hashimi
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·Colleen A KellenbergerMing C Hammond
Apr 8, 2015·Proceedings of the National Academy of Sciences of the United States of America·James W NelsonRonald R Breaker
Jun 4, 2015·Nature Communications·Alexey RozovGulnara Yusupova
May 7, 2016·Journal of the American Chemical Society·Timothy J WilsonDavid M J Lilley

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