Characterisation of an aptamer against the Runt domain of AML1 (RUNX1) by NMR and mutational analyses. Issue 2 (2nd January 2018) - Takada, Kenta
Abstract : Since the invention of systematic evolution of ligands by exponential enrichment, many short oligonucleotides (or aptamers) have been reported that can bind to a wide range of target molecules with high affinity and specificity. Previously, we reported an RNA aptamer that shows high affinity to the Runt domain (RD) of the AML1 protein, a transcription factor with roles in haematopoiesis and immune function. From kinetic and thermodynamic studies, it was suggested that the aptamer recognises a large surface area of the RD, using numerous weak interactions. In this study, we identified the secondary structure by nuclear magnetic resonance spectroscopy and performed a mutational study to reveal the residue critical for binding to the RD. It was suggested that the large contact area was formed by a DNA‐mimicking motif and a multibranched loop, which confers the high affinity and specificity of binding. Abstract : An RNA aptamer against the Runt domain (RD) of AML1 has been shown previously to recognize a large surface area of the RD, using numerous weak interactions. In this study, we show that the large contact area was formed by a DNA‐mimicking motif and a multibranched loop, which confers the high affinity and specificity of the binding of the aptamer to the RD.