- 學位論文
胃幽門螺旋桿菌蛋白HP1442的結合區域與其受質之識別
Identification of Binding Ligands and Association Region of HP1442 from Helicobacter pylori
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摘要
胃幽門螺旋桿菌早在原始人離開非洲之前就已存在於胃中，並藉由人類的遷徙而散播到世界各地。目前，全世界仍有超過百分之五十的人口受到此菌種的感染，有時會造成消化性潰瘍或胃癌等嚴重疾病。雖然胃幽門螺旋桿菌已成功的發展出對抗極酸環境的特性，使其能夠在如此惡劣的環境之下，長期的生存在人類的胃壁黏膜上，但在其基因組內，卻只有少數能夠隨著環境改變而調節基因表現的調控因子。碳源儲存調控因子(CsrA)廣泛存在於許多不同的菌種中，為一核醣核酸鍵結蛋白，其調控機制屬於後轉錄層級，主要影響基因表現來適應環境大規模的改變。而在胃幽門螺旋桿菌中，亦可發現碳源儲存調控因子的蹤跡(HP1442)，但其調控的基因以及作用的目標序列尚不清楚。在此，我們利用SELEX (systematic evolution of ligands by exponential enrichment)的技術來辨識出HP1442的受質，其中大部分都包含AGGA的序列區段；並且收集一系列HP1442與受質混合後的 HSQC光譜，進而推測出HP1442與受質相互作用的區塊。
並列摘要
Helicobacter pylori was already present in the stomach of primitive humans as they left Africa and spread through the world. Today, it still chronically infects more than 50% of the human population, causing, in some cases, severe diseases such as peptic ulcers and stomach cancer. Although successful life-lasting habitation of such harsh environment is made by combination of several special characteristic of H. pylori to against the challenge of the extreme acidity, it possesses relatively few transcriptional regulators. The carbon storage regulator (CsrA) family of RNA-binding proteins are global post-transcriptional regulators that mediate extensive changes in gene expression in bacteria. Various homologs are found in broad range of different species, including H. pylori. However, the regulated genes and target sequences by CsrA homolog (HP1442) in H. pylori are still unclear. Ligands of HP1442 were identified from a combinational library using systematic evolution of ligands by exponential enrichment (SELEX). The SELEX derived sequences contained consensus AGGA elements. A series of 1H-15N heteronuclear single quantum coherence (HSQC) spectra with or without selected ligands were also acquired to find out the binding region of HP1442.
參考文獻
1. Alm, R. A., L. S. Ling, D. T. Moir, B. L. King, E. D. Brown, P. C. Doig, D. R. Smith, B. Noonan, B. C. Guild, B. L. deJonge, G. Carmel, P. J. Tummino, A. Caruso, M. Uria-Nickelsen, D. M. Mills, C. Ives, R. Gibson, D. Merberg, S. D. Mills, Q. Jiang, D. E. Taylor, G. F. Vovis, and T. J. Trust. 1999. Genomic-sequence comparison of two unrelated isolates of the human gastric pathogen Helicobacter pylori. Nature 397:176-80.
2. Altier, C., M. Suyemoto, and S. D. Lawhon. 2000. Regulation of Salmonella enterica serovar typhimurium invasion genes by csrA. Infect Immun 68:6790-7.
3. Altschul, S. F., W. Gish, W. Miller, E. W. Myers, and D. J. Lipman. 1990. Basic local alignment search tool. J Mol Biol 215:403-10.
4. Ang, S., Y. T. Horng, J. C. Shu, P. C. Soo, J. H. Liu, W. C. Yi, H. C. Lai, K. T. Luh, S. W. Ho, and S. Swift. 2001. The role of RsmA in the regulation of swarming motility in Serratia marcescens. J Biomed Sci 8:160-9.
5. Baker, C. S., I. Morozov, K. Suzuki, T. Romeo, and P. Babitzke. 2002. CsrA regulates glycogen biosynthesis by preventing translation of glgC in Escherichia coli. Mol Microbiol 44:1599-610.