Molecular recognition in the FMN-RNA aptamer complex
Molecular recognition in the FMN-RNA aptamer complex
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DOI：
10.1006/jmbi.1996.0263
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发表时间：
1996-05-10
影响因子：
5.6
通讯作者：
Patel, DJ
中科院分区：
文献类型：
--
作者：
Fan, P;Suri, AK;Patel, DJ
我们报告的组合NMR分子动力学计算方法，解决了溶液结构的复杂的黄素单核苷酸（FMN）绑定到保守的内部循环段的35个核苷酸的RNA适体，通过体外选择确定。FMN-RNA适体复合物表现出非常好的分辨NMR光谱，其已经在复合物中含有均匀的C-13，N-15标记的RNA适体的样品上应用二维，三维和四维杂波NMR技术后分配。通过一种新的通过键NMR技术的分配鸟嘌呤亚氨基和腺嘌呤氨基质子在RNA环段的分配的援助。保守的内环通过形成碱基对错配和碱基三联体形成复合物，FMN的异咯嗪环插入G之间的螺旋。G不匹配和G。联合三垒识别特异性与FMN的异咯嗪环的尿嘧啶样边缘与腺嘌呤在嵌入位点的Hoogsteen边缘的氢键结合有关。在复合物中插入的异咯嗪环与其相邻的碱基-三重平台之间存在显著的重叠。内环中其余保守残基参与两个G .一个错配的复合体。拉链式内环和侧翼茎区形成一个连续的螺旋，除了一个非保守的腺嘌呤，它从螺旋中环出以促进碱基三重体的形成。我们的FMN-RNA适体复合物的溶液结构是我们所知的RNA适体复合物的第一个结构，并概述了其他RNA内环和发夹环所共有的折叠原理，以及化学生物学中模拟自我复制系统所共有的分子识别原理。(C)1996年学术出版社
We report on a combined NMR-molecular dynamics calculation approach that has solved the solution structure of the complex of flavin mononucleotide (FMN) bound to the conserved internal loop segment of a 35 nucleotide RNA aptamer identified through in vitro selection. The FMN-RNA aptamer complex exhibits exceptionally well-resolved NMR spectra that have been assigned following application of two, three and four-dimensional heteronuclear NMR techniques on samples containing uniformly C-13,N-15-labeled RNA aptamer in the complex. The assignments were aided by a new through-bond NMR technique for assignment of guanine imino and adenine amino protons in RNA loop segments. The conserved internal loop zippers up through the formation of base-pair mismatches and a base-triple on complex formation with the isoalloxazine ring of FMN intercalating into the helix between a G . G mismatch and a G . U . A base-triple. The recognition specificity is associated with hydrogen bonding of the uracil like edge of the isoalloxazine ring of FMN to the Hoogsteen edge of an adenine at the intercalation site. There is significant overlap between the intercalated isoalloxazine ring and its adjacent base-triple platform in the complex. The remaining conserved residues in the internal loop participate in two G . A mismatches in the complex. The zippered-up internal loop and flanking stem regions form a continuous helix with a regular sugar-phosphate backbone except at a non-conserved adenine, which loops out of the helix to facilitate base-triple formation. Our solution structure of the FMN-RNA aptamer complex is to our knowledge the first structure of an RNA aptamer complex and outlines folding principles that are common to other RNA internal and hairpin loops, and molecular recognition principles common to model self-replication systems in chemical biology. (C) 1996 Academic Press Limited