Solution structure of an informationally complex high-affinity RNA aptamer to GTP

RNA
James M CarothersJ W Szostak

Abstract

Higher-affinity RNA aptamers to GTP are more informationally complex than lower-affinity aptamers. Analog binding studies have shown that the additional information needed to improve affinity does not specify more interactions with the ligand. In light of those observations, we would like to understand the structural characteristics that enable complex aptamers to bind their ligands with higher affinity. Here we present the solution structure of the 41-nt Class I GTP aptamer (K(d) = 75 nM) as determined by NMR. The backbone of the aptamer forms a reverse-S that shapes the binding pocket. The ligand nucleobase stacks between purine platforms and makes hydrogen bonds with the edge of another base. Interestingly, the local modes of interaction for the Class I aptamer and an RNA aptamer that binds ATP with a K(d) of 6 microM are very much alike. The aptamers exhibit nearly identical levels of binding specificity and fraction of ligand sequestered from the solvent (81%-85%). However, the GTP aptamer is more informationally complex (approximately 45 vs. 35 bits) and has a larger recognition bulge (15 vs. 12 nucleotides) with many more stabilizing base-base interactions. Because the aptamers have similar modes of ligand binding, we co...Continue Reading

References

Sep 11, 1992·Nucleic Acids Research·E P NikonowiczA Pardi
Jan 1, 1989·Methods in Enzymology·J F Milligan, O C Uhlenbeck
Apr 5, 1986·Journal of Molecular Biology·T D SchneiderA Ehrenfeucht
Mar 11, 1994·Science·R D JenisonB Polisky
Jul 14, 1995·Journal of Molecular Biology·F H Allain, G Varani
Aug 5, 1993·Nature·M Sassanfar, J W Szostak
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
May 10, 1996·Journal of Molecular Biology·P FanD J Patel
Nov 5, 1997·Journal of Molecular Biology·T DieckmannJ Feigon
Oct 1, 1995·Chemistry & Biology·B E EatonD A Zichi
Feb 5, 2000·Science·T Hermann, D J Patel
Mar 15, 2000·Biochemistry·N H BergmanD P Bartel
Jun 29, 2000·Annual Review of Biochemistry·P B Moore
Feb 1, 1996·Accounts of Chemical Research·J R Lorsch, J W Szostak
Dec 26, 2001·Nucleic Acids Research·Uma NagaswamyGeorge E Fox
Feb 28, 2002·Methods : a Companion to Methods in Enzymology·P J Lukavsky, J D Puglisi
Jul 12, 2002·Nature·Bruce A Sullenger, Eli Gilboa
Aug 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jonathan H Davis, Jack W Szostak
Sep 5, 2002·Proteins·Natasja BrooijmansIrwin D Kuntz
Jan 30, 2003·RNA·Szilvia SzépPeter B Moore
Feb 5, 2003·Journal of Magnetic Resonance·Charles D SchwietersG Marius Clore
Jun 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Bernd HoffmannPascale Legault
Jun 13, 2003·Nature·Jack W Szostak
Oct 3, 2003·Chembiochem : a European Journal of Chemical Biology·Martina Rimmele
Apr 22, 2004·Journal of the American Chemical Society·James M CarothersJack W Szostak
Dec 2, 2004·Journal of the American Chemical Society·Matthew W L LauPeter J Unrau
Feb 11, 2005·RNA·Thomas C Leeper, Gabriele Varani
Sep 3, 2005·Chembiochem : a European Journal of Chemical Biology·Michael P LathamArthur Pardi
Nov 8, 2005·Nature Structural & Molecular Biology·Erik A SchultesDavid P Bartel

❮ Previous
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Citations

Oct 12, 2010·Biochemistry·Jinwei ZhangAdrian R Ferré-D'Amaré
Jun 1, 2010·Nucleic Acids Research·Elisa BiondiDonald H Burke
Oct 2, 2009·Journal of Molecular Evolution·Michael YarusRob Knight
Mar 27, 2007·Cold Spring Harbor Symposia on Quantitative Biology·S D GilbertR T Batey
Sep 1, 2007·Expert Opinion on Drug Discovery·Aniela WochnerMartina Rimmele
Jul 2, 2011·Bioorganic & Medicinal Chemistry Letters·Shun NakanoTakashi Morii
Oct 26, 2010·Journal of Biotechnology·Wenjie ShuShengqi Wang
Jul 4, 2009·Journal of the American Chemical Society·Mark P ElenkoAntoine M van Oijen
Sep 4, 2007·Trends in Biochemical Sciences·Catherine A WakemanCharles E Dann
Jul 28, 2006·Chembiochem : a European Journal of Chemical Biology·Jonas NoeskeJens Wöhnert
Aug 25, 2009·Journal of Molecular Recognition : JMR·Jiro Kondo, Eric Westhof
Sep 17, 2015·Biomolecular NMR Assignments·Antje C WolterJens Wöhnert
May 16, 2014·RNA Biology·Edward A Curtis, David R Liu
Jun 18, 2010·Methods : a Companion to Methods in Enzymology·Nathan J Riccitelli, Andrej Lupták
Jul 6, 2016·Frontiers in Chemistry·Franziska Pfeiffer, Günter Mayer
Jun 25, 2016·Methods : a Companion to Methods in Enzymology·Chuhern Hwang, James M Carothers
Aug 17, 2016·Proceedings of the National Academy of Sciences of the United States of America·David P Horning, Gerald F Joyce
Jun 6, 2013·Journal of the American Chemical Society·Yuri ImaizumiNaoki Sugimoto
Aug 28, 2013·Proceedings of the National Academy of Sciences of the United States of America·José I JiménezIrene A Chen
Jul 7, 2018·Nature Reviews. Drug Discovery·Katherine Deigan WarnerKevin M Weeks
Dec 15, 2017·Current Protocols in Chemical Biology·Annamaria RuscitoMaria C DeRosa
Apr 29, 2019·Biomolecular NMR Assignments·Antje C WolterJens Wöhnert
Oct 9, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Natalia Komarova, Alexander Kuznetsov
Nov 23, 2019·Nucleic Acids Research·Elke Duchardt-FernerJens Wöhnert
Aug 25, 2007·Chemical Reviews·Michael FamulokGünter Mayer
Jun 17, 2021·Nucleic Acids Research·Tereza StreckerováEdward A Curtis
May 18, 2021·The New Phytologist·Constantine GaragounisKalliope K Papadopoulou
Mar 5, 2011·Journal of the American Chemical Society·Shun NakanoTakashi Morii
Sep 7, 2018·ACS Combinatorial Science·Maeling J N TappValeria T Milam
Dec 31, 2019·Journal of the American Chemical Society·Fabio ChizzoliniAndrej Lupták
Jun 15, 2006·Journal of the American Chemical Society·James M CarothersJack W Szostak
Sep 23, 2006·Science·Daniel J Klein, Adrian R Ferré-D'Amaré

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