Crystallographic Pursuit of a Protein-RNA Aptamer Complex

Only a few of the aptamers designed to selectively target proteins have been structurally characterized, such as those that target thrombin, von Willebrand factor, Plasmodium falciparum lactate dehydrogenase, interleukin 6, and platelet-derived growth factor B. Most of these aptamers are composed of DNA and were designed as therapeutics/diagnostics for targets found in human plasma. Recently, the crystal structure of a complex between an RNA aptamer and an intracellular target, G protein-coupled receptor kinase 2, was determined. Herein is described the overall approach used to isolate crystals that would allow the identification of the key interactions between aptamer and kinase. These strategies may be useful in structural characterization of other SELEX-generated RNA aptamer complexes.