A computational investigation on the connection between dynamics properties of ribosomal proteins and ribosome assembly.
A computational investigation on the connection between dynamics properties of ribosomal proteins and ribosome assembly.
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DOI：
10.1371/journal.pcbi.1002530
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发表时间：
2012
影响因子：
4.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Burton B;Zimmermann MT;Jernigan RL;Wang Y
在过去的50年里，人们对核糖体的蛋白质和RNA成分的组装进行了广泛的研究，实验证据表明，原核核糖体蛋白在组装过程中会发生构象变化。然而，到目前为止，还没有研究试图阐明这些构象变化。本研究利用计算方法来分析蛋白质动力学，并研究核糖体组装过程中这些蛋白质的动力学和结合之间的联系。已知核糖体蛋白是带正电的，我们发现r蛋白中带正电残基的比例大约是普通蛋白的两倍：大肠杆菌中Lys+Arg的比例为18.7%，嗜热杆菌中为21.2%。此外，正残基占RNA接触残基的很大比例：大肠杆菌为39%，嗜热杆菌为46%。这证实了已知的核糖体组装中电荷-电荷相互作用的重要性。我们通过原子分子动力学模拟研究了大肠杆菌和嗜热T. 30S亚基中在组装早期结合的三种初级蛋白（S15、S17和S20）的动力学，随后使用弹性网络模型研究了所有r-蛋白。分子动力学模拟表明，溶剂暴露蛋白（S15和S17）倾向于采用比rna嵌入蛋白（S20）更稳定的溶液构象。我们还发现，与其他残基相比，接触16S rRNA的蛋白质残基通常更具流动性。这是因为有较大比例的接触残留物位于柔性环区域。通过使用计算效率更高的弹性网络模型，我们表明这种趋势适用于大多数30S r-蛋白。核糖体是复杂的细胞机器，在细胞中合成新的蛋白质。准确有效地组装核糖体蛋白（r-protein）和核糖体RNA （rRNA）以形成功能性核糖体对于细胞生长、代谢反应和其他细胞过程是重要的。此外，一些抗菌药物在细菌核糖体的构建过程中被认为是靶向的。因此，核糖体组装多年来一直是一个活跃的研究课题，因为了解组装机制可以提供对许多其他细胞过程中重要的蛋白质/RNA识别的见解，以及优化抗菌治疗的开发。迄今为止，实验研究对装配过程的了解仍然有限。为了进一步了解组装过程，我们通过计算研究了r-蛋白在组装过程中表现出的动态特性，以及动力学、物理特性和结合倾向之间的关系。我们观察到r-蛋白和rRNA之间显著的带电相互作用。我们还发现接触残留物和它们的动态流动性之间有很强的相关性。与其他残基相比，与rRNA接触的蛋白质残基具有更强的流动性。我们还将r蛋白在完全组装的核糖体中的位置与其在结合前对大构象变化的易感性联系起来。
Assembly of the ribosome from its protein and RNA constituents has been studied extensively over the past 50 years, and experimental evidence suggests that prokaryotic ribosomal proteins undergo conformational changes during assembly. However, to date, no studies have attempted to elucidate these conformational changes. The present work utilizes computational methods to analyze protein dynamics and to investigate the linkage between dynamics and binding of these proteins during the assembly of the ribosome. Ribosomal proteins are known to be positively charged and we find the percentage of positive residues in r-proteins to be about twice that of the average protein: Lys+Arg is 18.7% for E. coli and 21.2% for T. thermophilus. Also, positive residues constitute a large proportion of RNA contacting residues: 39% for E. coli and 46% for T. thermophilus. This affirms the known importance of charge-charge interactions in the assembly of the ribosome. We studied the dynamics of three primary proteins from E. coli and T. thermophilus 30S subunits that bind early in the assembly (S15, S17, and S20) with atomic molecular dynamic simulations, followed by a study of all r-proteins using elastic network models. Molecular dynamics simulations show that solvent-exposed proteins (S15 and S17) tend to adopt more stable solution conformations than an RNA-embedded protein (S20). We also find protein residues that contact the 16S rRNA are generally more mobile in comparison with the other residues. This is because there is a larger proportion of contacting residues located in flexible loop regions. By the use of elastic network models, which are computationally more efficient, we show that this trend holds for most of the 30S r-proteins. Ribosomes are complex cellular machines that synthesize new proteins in the cell. The accurate and efficient assembly of ribosomal proteins (r-proteins) and ribosomal RNA (rRNA) to form a functional ribosome is important for cell growth, metabolic reactions, and other cellular processes. Additionally, some antibacterial drugs are believed to target the bacterial ribosome during its construction. Hence, ribosomal assembly has been an active research topic for many years because understanding the assembly mechanisms can provide insight into protein/RNA recognitions important in many other cellular processes, as well as optimize the development of antibacterial therapeutics. Experimental studies thus far have provided still limited understanding about the assembly process. To further understand the assembly process, we have computationally studied the dynamic properties that r-proteins exhibit during assembly and the relationship between dynamics, physical properties, and binding propensity. We observe significant charged interactions between r-proteins and rRNA. We also detect a strong correlation between contact residues and their dynamic mobilities. Protein residues contacting with rRNA are observed to be more mobile in comparison with other residues. We also relate the location of the r-protein in the fully assembled ribosome to its susceptibility for large conformational changes prior to binding.
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影响因子：
5.6
作者：
Dutca, Laura M.;Culver, Gloria M.
通讯作者：
Culver, Gloria M.
影响因子：
2.9
作者：
GOLDEN, BL;HOFFMAN, DW;WHITE, SW
通讯作者：
WHITE, SW
影响因子：
2.9
作者：
Almlof, Martin;Ander, Martin;Aqvist, Johan
通讯作者：
Aqvist, Johan
DOI：
10.1016/s1359-0278(97)00024-2
发表时间：
1997-01-01
期刊：
FOLDING & DESIGN
影响因子：
--
作者：
Bahar, I;Atilgan, AR;Erman, B
通讯作者：
Erman, B
影响因子：
56.9
作者：
Culver, GM;Cate, JH;Noller, HF
通讯作者：
Noller, HF