A Small Cyclic β-Hairpin Peptide Mimics the Rbfox2 RNA Recognition Motif and Binds to the Precursor miRNA 20b.,ChemBioChem

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A Small Cyclic β-Hairpin Peptide Mimics the Rbfox2 RNA Recognition Motif and Binds to the Precursor miRNA 20b.
ChemBioChem ( IF 2.6 ) Pub Date : 2019-02-15 , DOI: 10.1002/cbic.201800645
Yi-Ting Sun ₁ , Matthew D Shortridge ₁ , Gabriele Varani ₁

Affiliation

The RNA recognition motif (RRM), which is the most abundant RNA-binding motif in eukaryotes, is a well-structured domain of about 90 amino acids, yet the β2β3 hairpin, corresponding to strands 2 and 3 of the β-sheet, and the intervening loop make essential interactions with RNA in many RRM complexes. A series of small cyclic peptide mimics of the β2β3 hairpin of Rbfox2 protein that recognize the terminal loop of precursor miR-20b have been designed to investigate whether the full RNA-binding protein can be mimicked with a minimal structurally preorganized peptide. Within a small library of seven cyclic peptides, a peptide with low-micromolar affinity for the miR-20b precursor was found. NMR spectroscopy titration data suggest that this peptide specifically targets the apical loop of pre-miR-20b. This work shows that it is possible to mimic RNA-binding proteins with designed stable peptides, which provide a starting point for designing or evolving small peptide mimetics of RRM proteins.

中文翻译：

一个小的环状β-发夹肽模拟Rbfox2 RNA识别基序，并与前体miRNA 20b结合。

RNA识别基序（RRM）是真核生物中最丰富的RNA结合基序，它是结构良好的结构域，包含约90个氨基酸，但β2β3发夹对应于β-折叠的链2和3，以及中间的环与许多RRM复合物中的RNA进行了必不可少的相互作用。已经设计了一系列识别前体miR-20b末端环的Rbfox2蛋白的β2β3发夹结构的小环肽模拟物，以研究是否可以用最小的结构预组织肽模拟完整的RNA结合蛋白。在一个由七个环状肽组成的小文库中，发现了一种对miR-20b前体具有低微摩尔亲和力的肽。NMR光谱滴定数据表明，该肽特异性靶向pre-miR-20b的顶端环。

更新日期：2019-02-15

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