Comprehensive features of natural and in vitro selected GNRA tetraloop-binding receptors.
Comprehensive features of natural and in vitro selected GNRA tetraloop-binding receptors.
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DOI：
10.1093/nar/gkm1048
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发表时间：
2008-03
影响因子：
14.9
通讯作者：
Jaeger L
中科院分区：
文献类型：
--
作者：
Geary C;Baudrey S;Jaeger L
小螺旋受体对GNRA四环的特异性修饰是大核酶中最广泛的长程包装相互作用之一。然而，与GYRA和GAAA四环相反，在自然界中很少有GNRA/受体相互作用涉及GGAA四环。一种新的在体外选择方案的基础上的刚性自组装tectoRNA支架设计用于隔离分子间相互作用与A-未成年人的图案产生了新的GGAA四环结合受体的亲和力在纳摩尔范围内。所选受体之一是新的12 nt RNA基序（CCUGUG... AUCUGG），其以显著的特异性和亲和力识别GGAA四环发夹。它的物理和化学特性与已被充分研究的'11nt' GAAA四环受体基序相当。第二个特异性较低的基序（CCCAGCCC... GAUAGGG）结合GGRA四环，似乎与IC 3组四环受体相关。突变、热力学和比较结构分析表明，天然和体外选择的GNRA受体基本上可以分为两大类GNRA结合剂。提出了关于GNRA和A-次要RNA-RNA相互作用的进化、识别和结构模块性的新见解。
Specific recognitions of GNRA tetraloops by small helical receptors are among the most widespread long-range packing interactions in large ribozymes. However, in contrast to GYRA and GAAA tetraloops, very few GNRA/receptor interactions have yet been identified to involve GGAA tetraloops in nature. A novel in vitro selection scheme based on a rigid self-assembling tectoRNA scaffold designed for isolation of intermolecular interactions with A-minor motifs has yielded new GGAA tetraloop-binding receptors with affinity in the nanomolar range. One of the selected receptors is a novel 12 nt RNA motif, (CCUGUG … AUCUGG), that recognizes GGAA tetraloop hairpin with a remarkable specificity and affinity. Its physical and chemical characteristics are comparable to those of the well-studied ‘11nt’ GAAA tetraloop receptor motif. A second less specific motif (CCCAGCCC … GAUAGGG) binds GGRA tetraloops and appears to be related to group IC3 tetraloop receptors. Mutational, thermodynamic and comparative structural analysis suggests that natural and in vitro selected GNRA receptors can essentially be grouped in two major classes of GNRA binders. New insights about the evolution, recognition and structural modularity of GNRA and A-minor RNA–RNA interactions are proposed.
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