氨酰-tRNA合成酶结构域的进化研究
文献类型：学位论文
| 作者 | 唐素妮 |
| 学位类别 | 博士 |
| 答辩日期 | 2008-06 |
| 授予单位 | 中国科学院研究生院 |
| 授予地点 | 北京 |
| 导师 | 黄京飞 |
| 关键词 | 类氨酰-tRNA合成酶 II类氨酰-tRNA合成酶 结构域 分子进化 |
| 其他题名 | Evolution of Aminoacyl-tRNA Synthetase Domains |
| 学位专业 | 动物学 |
| 中文摘要 | 氨酰-tRNA合成酶(Aminoacyl-tRNA synthetases, aaRS)是一类在蛋白质生物合成中具有重要作用的酶，它可以活化氨基酸，并与相应的tRNA相识别，使得基因序列能够被精确的翻译成蛋白质序列，保证了生命体的严谨性和多样性。通常，每一类aaRS都包含有一个催化核心结构域(Catalytic central domain, CCD)和一个结合反密码子的结构域(Anticodon-binding domain, ABD)。大量研究显示，细菌与真核生物中的许多aaRS在一些细菌与真核生物中的基因进化机制与模式、氨酰化途径、结构与功能的进化模式等方面往往有着明显的差异。通过对这些差异的深入研究，对于理解蛋白质的结构、功能的进化将是非常有帮助的。虽然，造成这些差异的本质，目前仍不清楚，但是，所有的这些差异似乎提示，在细菌与真核生物的一些基本生命活动过程中的某些方面，可能还存在着目前尚未被人们所认识到的较大差异。 甘氨酰-tRNA合成酶(Glycyl-tRNA synthetase，GlyRS)在基因组中存在着两种寡聚体形式，即α2β2四聚体和α2二聚体。本研究的结果显示，四聚体和二聚体GlyRS的ABD并不同源，而它们的CCD却具有共同的起源。在进化过程中，由于基因的融合，二聚体GlyRS的ABD融合到α亚基上CCD后的C-末端，而四聚体GlyRS的ABD则加在了β亚基的C-末端。通常，同一物种中只存在一种寡聚体形式的GlyRS，但是在Magnetospirillum magnetotacticum基因组中同时存在GlyRS的两种寡聚体形式，并有多个同源的结构域，而这些同源的结构域很可能来源于不同的基因组。二聚体GlyRS存在于细菌、古细菌和真核生物中，而四聚体GlyRS仅在大多数细菌中发现。在从细菌到真核生物的进化过程中，GlyRS可能经历了一个复杂的进化历程。频繁的基因丢失和获得事件导致了GlyRS分布的差异。水平基因转移是四聚体GlyRS进化的一个主要因素。大量的细菌基因水平转移导致四聚体GlyRS基因可在植物中表达，而在动物中形成假基因。 通常，由于aaRS-I和aaRS-II具有不同的结构和催化机制，它们被认为在进化上没有联系。虽然，苯丙氨酰-tRNA合成酶(phenylalanyl-tRNA synthetase, PheRS)属于aaRS-II，但它的催化机制却类似于aaRS-I。结构域的进化分析表明，细菌、古细菌和真核生物的PheRS具有明显不同的结构，因而导致从细菌到真核生物的进化过程中，PheRS和 tRNAPhe间的识别机制发生了变化。序列分析表明，PheRS的结构域(包括CCD、ABD及其它结构域)与aaRS-I的某些结构域同源，因此，在进化上，PheRS是aaRS-II与aaRS-I之间联系的纽带。这些结果表明，在进化的过程中，aaRS-I和aaRS-II可能是由同一个共同的祖先CCD经过可变剪接和插入演化而来的，结构域间的不同组合导致aaRS-I和aaRS-II在结构和催化机制上的显著差异。 |
| 英文摘要 | Aminoacyl-tRNA synthetase (aaRS) is a key enzyme during protein biosynthesis, which can activate and transfer the corresponding amino acids to its cognate tRNA. This process is very important to make gene be accurately translated into protein and keep the stability and variety of the lives. Generally, each aaRS contains a catalytic central domain (CCD) and an anticodon-binding domain (ABD). A lot of studies show that the gene evolutionary mechanisms and modes, aminoacylation routes, and evolutionary mechanisms in structure and function of many aminoacyl-tRNA synthetases (aaRS), are diverse in some bacteria and eukaryotes. Thus, further studies on these diversities will be useful in understanding protein structural and functional evolution. Although the essential mechanism responsible for these diversities is not understood, these diversities suggest that certain aspects of the biological processes between bacteria and eukaryotes require further study. There are two oligomeric types of glycyl-tRNA synthetases (GlyRSs) in genome, the α2β2 tetramer and α2 dimer. Here, we showed that the anticodon-binding domains (ABDs) of dimeric and tetrameric GlyRSs are non-homologous, although their catalytic central domains (CCDs) are homologous. The dimeric GlyRS_ABD is fused to the C-terminal of CCD in α-subunit, but the tetrameric GlyRS_ABD is to the C-terminal in β-subunit during evolution. Generally, one species only contains one oligomeric type of GlyRS, but the both oligomeric GlyRSs with the multiple homologous domains can be observed in Magnetospirillum magnetotacticum genome, nevertheless, these homologous domains are probably from different genomes. The dimeric GlyRS can be observed in bacteria, archaebacteria and eukaryotes, but the tetrameric GlyRS only exists in most bactetia. GlyRS may have undergone a complex process during the evolution from bacteria to eukaryotes. Frequency gene loss and gain events could result in the different distribution of GlyRS. Gene horizontal transfer is a major factor in tetrameric GlyRS evolution. A number of gene horizontal transfers from bacteria led to the tetrameric GlyRS gene can express in plants and become pseudogenes in animals. Usually, the two class aminoacyl-tRNA synthetases (aaRSs) with different structures and catalytic mechanisms, the class I (aaRS-I) and II (aaRS-II), are suggested to be unrelated in evolution. However, the catalytic mechanism of phenylalanyl-tRNA synthetase (PheRS) belonging to the aaRS-II is similar to that of the aaRS-I. The domain evolutionary analyses show that PheRSs in bacteria and archaebacteria/eukaryotes have the striking different structures, which could result in different recognition mechanisms between PheRS and tRNAPhe during evolution from bacteria, archaebacteria to eukaryotes. Sequence analyses indicate that the PheRS domains, including the catalytic central domain (CCD), the anticodon-binding domain (ABD) and other domains, are homologous with some domains of aaRS-I, thus, the PheRS could be related to the both aaRS-II and aaRS-I in evolution. The results suggest that the aaRS-I and aaRS-II are probably from a common ancestor CCD by gene alternative splicing and insertion during evolution, although the various combinations of these domains have resulted in the obviously difference between the aaRS-I and aaRS-II in structure and in catalytic mechanism. |
| 语种 | 中文 |
| 公开日期 | 2010-10-14 |
| 源URL | [http://159.226.149.42:8088/handle/152453/6087]  |
| 专题 | 昆明动物研究所_结构生物信息学 |
| 推荐引用方式 GB/T 7714 | 唐素妮. 氨酰-tRNA合成酶结构域的进化研究[D]. 北京. 中国科学院研究生院. 2008. |
入库方式： OAI收割
来源：昆明动物研究所
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