Solution structure of an informationally complex high-affinity RNA aptamer to GTP
Open accessAbstract
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 μM 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 (~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 conclude that the stabilizing structural elements in the Class I aptamer are responsible for much of the difference in K d . These results are consistent with the hypothesis that increasing the number of intra-RNA interactions, rather than adding specific contacts to the ligand, is the simplest way to improve binding affinity.
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Greater stability is one of the factors promoting greater functional activity in RNA aptamers.
“Greater stability is one of the factors promoting greater functional activity in RNA aptamers (29,30).”
From Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences (2012) · cites this paper as [30]
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- Authors
- CAROTHERS, J. M., DAVIS, J. H., CHOU, J. J., & SZOSTAK, J. W.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Corresponding author
- SZOSTAK, JACK W.
- Venue
- RNA
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-02-28
- Volume
- 12
- Issue
- 4
- Pages
- 567-579
- ISSN
- 1355-8382 (ISSN-L)
- 1469-9001
- PMC
- PMC1421093
- OpenAlex
- W2162296614
- Cited by
- 78
- References
- 52
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 6 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 2.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Science Foundation
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of General Medical Sciences (GM53936, GM17438, F32GM017438, R01GM053936)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced biosensing and bioanalysis techniques
- Keywords
- RNA aptamers, GTP binding, solution structure, binding affinity, information complexity, hydrogen bonding, ATP binding, base-base interactions, ligand specificity, NMR structure
- MeSH terms
- Base Sequence, Guanosine Triphosphate, Nucleic Acid Conformation, RNA, Nuclear Magnetic Resonance, Biomolecular, Aptamers, Nucleotide
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