Characterisation of an aptamer against the Runt domain of AML1 (RUNX1) by NMR and mutational analyses. Issue 2 (2nd January 2018)

• Record Type: Journal Article
• Authors: Takada, Kenta; Amano, Ryo; Nomura, Yusuke; Tanaka, Yoichiro; Sugiyama, Shigeru; Nagata, Takashi; Katahira, Masato; Nakamura, Yoshikazu; Kozu, Tomoko; Sakamoto, Taiichi
• Is Part Of: FEBS open bio. Volume 8:Issue 2(2018)
• Page Start: 264
• Page End: 270
• Publication Date: 2018-01-02
• Subjects: AML1 -- aptamer -- Mutation -- NMR; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.12368
• Languages: English
• ISSNs: 2211-5463

Abstract

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.