Butcher S E, Dieckmann T, Feigon J
Department of Chemistry and Biochemistry, and Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569, USA.
EMBO J. 1997 Dec 15;16(24):7490-9. doi: 10.1093/emboj/16.24.7490.
The GAAA tetraloop receptor is an 11-nucleotide RNA sequence that participates in the tertiary folding of a variety of large catalytic RNAs by providing a specific binding site for GAAA tetraloops. Here we report the solution structure of the isolated tetraloop receptor as solved by multidimensional, heteronuclear magnetic resonance spectroscopy. The internal loop of the tetraloop receptor has three adenosines stacked in a cross-strand or zipper-like fashion. This arrangement produces a high degree of base stacking within the asymmetric internal loop without extrahelical bases or kinking the helix. Additional interactions within the internal loop include a U. U mismatch pair and a G.U wobble pair. A comparison with the crystal structure of the receptor RNA bound to its tetraloop shows that a conformational change has to occur upon tetraloop binding, which is in good agreement with previous biochemical data. A model for an alternative binding site within the receptor is proposed based on the NMR structure, phylogenetic data and previous crystallographic structures of tetraloop interactions.
GAAA四环受体是一种11个核苷酸的RNA序列,它通过为GAAA四环提供特定的结合位点,参与多种大型催化RNA的三级折叠。在此,我们报道了通过多维异核磁共振波谱解析得到的分离四环受体的溶液结构。四环受体的内环有三个腺苷以跨链或拉链状方式堆积。这种排列在不对称内环内产生了高度的碱基堆积,没有额外的螺旋外碱基或使螺旋扭结。内环内的其他相互作用包括一个U·U错配碱基对和一个G·U摆动碱基对。将该受体RNA与其四环结合的晶体结构进行比较表明,四环结合时会发生构象变化,这与先前的生化数据高度一致。基于NMR结构、系统发育数据和先前四环相互作用的晶体学结构,提出了受体内部一个替代结合位点的模型。