Short talk 2
GTP binding by a topologically complex G-quadruplex in a GTP aptamer

Presenting Author: Helena Stafflinger

Goethe - Universität Frankfurt, Molekulare Biowissenschaften, Max-von-Laue Str. 9, 60438 Frankfurt, DE, stafflinger@bio.uni-frankfurt.de

Author(s)
Helena Stafflinger¹, Dr. Elke Duchardt-Ferner¹, Prof. Dr. Ronald Micura², Prof. Dr. Hermann Schindelin³, Prof. Dr. Jens Wöhnert¹

RNA molecules are capable of forming complex secondary and tertiary structures which can serve as binding sites for a variety of small molecule ligands, proteins or other RNAs. The structural complexity of these motifs is often the basis for a high affinity and specificity of RNA-ligand interactions. However, it is still very difficult to accurately predict RNA three-dimensional structures due to the still small number of experimentally determined RNA structures available as training data.
For GTP as the ligand a large number of in vitro selected RNA aptamers are known which differ widely in sequence, secondary structure and ligand binding affinity and specificity. Here we report a 1.6 Å crystal structure of the class V-GTP aptamer bound to GTP, revealing a topologically complex three-layered G-quadruplex. The GTP ligand is directly incorporated into one G-quadruplex layer. The quadruplex is only formed upon ligand binding and is further stabilized by a variety of non-canonical interactions. Importantly, the structure does not correspond to typical G-quadruplex topologies with G-tracts that are separated by short single-stranded loops. Instead, in our structure the G-tracts are separated by an A-form double helix.
This complex tertiary folding could not be predicted from the sequence and the previously determined secondary structure and therefore raises the question, if this or similar RNA folds occur in other functional RNAs in biological systems.

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