Vibrational dynamics of transfer RNAs: Comparison of the free and synthetase-bound forms
Vibrational dynamics of transfer RNAs: Comparison of the free and synthetase-bound forms
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DOI：
10.1006/jmbi.1998.1978
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发表时间：
1998-09-04
影响因子：
5.6
通讯作者：
Jernigan, RL
中科院分区：
文献类型：
--
作者：
Bahar, I;Jernigan, RL
的振动动力学的转移RNA，无论是自由的，和复杂的同源合成酶，使用一个模型（高斯网络模型），最近被证明是令人满意地描述折叠蛋白质的集体运动进行了分析。该方法类似于正常模式分析，主要的简化是不考虑残基特异性，这允许我们（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，以及（ii）在计算时间内获得这种大型系统的基本动力学信息，比常规方法短至少两个数量级模拟在局部尺度上，酵母tRNA（Phe）和tRNA（Asp）在游离状态下，以及tRNA（Gln）与氨酰-tRNA合成酶（GlnRS）复合物的波动计算与相应的晶体学B因子很好地一致。在全局范围内，在游离tRNA中鉴定了铰链弯曲区域，其包括D臂中的核苷酸US至C12、D环中的核苷酸G20至G22以及可变环中的核苷酸m（7）G46至C48（对于tRNA（Phe）），这与先前的观察结果一致。在自由形式中，受到最大幅度的与DNA相关的波动的两个区域，即反密码子区域和受体臂，同时是在与合成酶结合时其灵活性受到最严重抑制的区域，这表明它们对构象空间的采样促进了合成酶对它们的识别。同样，对复合物中GlnRS的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（所有这些残基都聚集在ATP结合位点附近）形成了控制酶的协同运动并由此控制催化功能的铰链弯曲区。另一方面，远端β-桶和tRNA受体结合结构域的区别在于它们在全局运动模式中的高迁移率，这是识别位点的典型特征，也在其他蛋白质中观察到。tRNA和GlnRS的大多数保守碱基和残基在分子的全局运动中受到严重的限制，这表明它们在稳定和调节全局运动中起作用。(C)北京：科学出版社.
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.