Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: Distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP Journal Article


Authors: Lin, C. H.; Patel, D. J.
Article Title: Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: Distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP
Abstract: Background: Structural studies by nuclear magnetic resonance (NMR) of RNA and DNA aptamer complexes identified through in vitro selection and amplification have provided a wealth of information on RNA and DNA tertiary structure and molecular recognition in solution. The RNA and DNA aptamers that target ATP (and AMP) with micromolar affinity exhibit distinct binding site sequences and secondary structures. We report below on the tertiary structure of the AMP-DNA aptamer complex in solution and compare it with the previously reported tertiary structure of the AMP-RNA aptamer complex in solution. Results: The solution structure of the AMP-DNA aptamer complex shows, surprisingly, that two AMP molecules are intercalated at adjacent sites within a rectangular widened minor groove. Complex formation involves adaptive binding where the asymmetric internal bubble of the free DNA aptamer zippers up through formation of a continuous six-base mismatch segment which includes a pair of adjacent three-base platforms. The AMP molecules pair through their Watson-Crick edges with the minor groove edges of guanine residues. These recognition G·A mismatches are flanked by sheared G·A and reversed Hoogsteen G·G mismatch pairs. Conclusions: The AMP-DNA aptamer and AMP-RNA aptamer complexes have distinct tertiary structures and binding stoichiometries. Nevertheless, both complexes have similar structural features and recognition alignments in their binding pockets. Specifically, AMP targets both DNA and RNA aptamers by intercalating between purine bases and through identical G·A mismatch formation. The recognition G·A mismatch stacks with a reversed Hoogsteen G·G mismatch in one direction and with an adenine base in the other direction in both complexes. It is striking that DNA and RNA aptamers selected independently from libraries of 1014 molecules in each case utilize identical mismatch alignments for molecular recognition with micromolar affinity within binding-site pockets containing common structural elements.
Keywords: molecular genetics; metabolism; rna; chemistry; dna; molecular sequence data; nucleotide sequence; magnetic resonance spectroscopy; nuclear magnetic resonance spectroscopy; base sequence; models, molecular; chemical structure; conformation; nucleic acid conformation; point mutation; macromolecule; macromolecular substances; adenosine phosphate; adenosine monophosphate; article; adaptive binding; amp-g recognition alignment; mismatch stabilized duplex; rectangular-shaped minor groove; two bound amps
Journal Title: Chemistry and Biology
Volume: 4
Issue: 11
ISSN: 1074-5521
Publisher: Elsevier Inc.  
Date Published: 1997-11-01
Start Page: 817
End Page: 832
Language: English
PUBMED: 9384529
PROVIDER: scopus
DOI: 10.1016/S1074-5521(97)90115-0
DOI/URL:
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Chin H Lin
    9 Lin
  2. Dinshaw J Patel
    445 Patel