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Vibrational dynamics of transfer RNAs: Comparison of the free and synthetase-bound forms

机译:转移RNA的振动动力学:游离和合成酶结合形式的比较

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The vibrational dynamics of transfer RNAs, both free, and complexed with the cognate synthetase, are analyzed using a model (Gaussian network model) which recently proved to satisfactorily describe the collective motions of folded proteins. The approach is similar to a normal mode analysis, with the major simplification that no residue specificity is taken into consideration, which permits us (i) to cast the problem into an analytical form applicable to biomolecular systems including about 10(3) residues, and (ii) to acquire information on the essential dynamics of such large systems within computational times at least two orders of magnitude shorter than conventional simulations. On a local scale, the fluctuations calculated for yeast tRNA(Phe) and tRNA(Asp) in the free state, and for tRNA(Gln) complexed with glutaminyl-tRNA synthetase (GlnRS) are in good agreement with the corresponding crystallographic B factors. On a global scale, a hinge-bending region comprising nucleotides US to C12 in the D arm, G20 to G22 in the D loop, and m(7)G46 to C48 in the variable loop (for tRNA(Phe)), is identified in the free tRNA, conforming with previous observations. The two regions subject to the largest amplitude anticorrelated fluctuations in the free form, i.e. the anticodon region and the acceptor arm are, at the same time, the regions that experience the most severe suppression in their flexibilities upon binding to synthetase, suggesting that their sampling of the conformational space facilitates their recognition by the synthetase. Likewise, examination of the global mode of motion of GlnRS in the complex indicates that residues 40 to 45, 260 to 270, 306 to 314, 320 to 327 and 478 to 485, all of which cluster near the ATP binding site, form a hinge-bending region controlling the cooperative motion, and thereby the catalytic function, of the enzyme. The distal beta-barrel and the tRNA acceptor binding domain, on the other hand, are distinguished by their high mobilities in the global modes of motion, a feature typical of recognition sites, also observed for other proteins. Most of the conserved bases and residues of tRNA and GlnRS are severely constrained in the global motions of the molecules, suggesting their having a role in stabilizing and modulating the global motion. (C) 1998 Academic Press. [References: 40]
机译:使用最近被证明可以令人满意地描述折叠蛋白的集体运动的模型(高斯网络模型)来分析游离的和与同源合成酶复合的转移RNA的振动动力学。该方法类似于正常模式分析,主要简化之处在于不考虑任何残基特异性,这使我们(i)将问题转换为适用于包括约10(3)个残基的生物分子系统的分析形式,并且(ii)在计算时间内获取有关此类大型系统的基本动力学信息,至少比传统仿真短两个数量级。在局部范围内,针对游离状态的酵母tRNA(Phe)和tRNA(Asp)以及与谷氨酰胺-tRNA合成酶(GlnRS)复合的tRNA(Gln)的波动与相应的晶体学B因子高度吻合。在全球范围内,确定了一个铰链弯曲区,该区域包含D臂中的US至C12核苷酸,D环中的G20至G22核苷酸和可变环中的m(7)G46至C48(对于tRNA(Phe))在游离的tRNA中,与以前的观察结果一致。在自由形式下,出现最大幅度抗相关波动的两个区域,即反密码子区域和受体臂,同时是在与合成酶结合后柔韧性受到最严重抑制的区域,这表明它们的采样构象空间中的一部分有助于它们被合成酶识别。同样,对复合物中GlnRS整体运动模式的检查表明,残基40至45、260至270、306至314、320至327和478至485(均聚集在ATP结合位点附近)形成铰链-弯曲区域控制酶的协同运动,从而控制酶的催化功能。另一方面,远侧的β-桶和tRNA受体结合域的特点是它们在整体运动模式中具有很高的运动能力,这是识别位点的典型特征,对于其他蛋白质也可以观察到。 tRNA和GlnRS的大多数保守碱基和残基在分子的整体运动中受到严格限制,表明它们在稳定和调节整体运动中具有作用。 (C)1998年学术出版社。 [参考:40]

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