Structural basis of RNA folding and recognition in an AMP–RNA aptamer complex

Abstract

THE catalytic properties of RNA1,2 and its well known role in gene expression and regulation are the consequence of its unique solution structures. Identification of the structural determinants of ligand recognition by RNA molecules is of fundamental importance for understanding the biological functions of RNA, as well as for the rational design of RNA sequences with specific catalytic activities3–6. Towards this latter end, Szostak et al.7,8 used in vitro selection techniques to isolate RNA sequences ('aptamers') containing a high-affinity binding site for ATP, the universal currency of cellular energy, and then used this motif to engineer ribozymes with polynucleotide kinase activity. Here we present the solution structure, as determined by multidimensional NMR spectroscopy and molecular dynamics calculations, of both uniformly and specifically 13C-, 15N-labelled 40-mer RNA containing the ATP-binding motif complexed with AMP. The aptamer adopts an L-shaped structure with two nearly orthogonal stems, each capped proximally by a G·G mismatch pair, binding the AMP ligand at their junction in a GNRA-like motif.

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Jiang, F., Kumar, R., Jones, R. et al. Structural basis of RNA folding and recognition in an AMP–RNA aptamer complex. Nature 382, 183–186 (1996). https://doi.org/10.1038/382183a0

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