請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17774完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 吳世雄(Shih-Hsiung Wu) | |
| dc.contributor.author | Cheng-Han Tsai | en |
| dc.contributor.author | 蔡承翰 | zh_TW |
| dc.date.accessioned | 2021-06-08T00:43:20Z | - |
| dc.date.copyright | 2015-09-17 | |
| dc.date.issued | 2015 | |
| dc.date.submitted | 2015-08-13 | |
| dc.identifier.citation | 1. International Human Genome Sequencing, C. (2004) Finishing the euchromatic sequence of the human genome. Nature 431, 931-945
2. Jensen, O. N. (2004) Modification-specific proteomics: characterization of post-translational modifications by mass spectrometry. Curr Opin Chem Biol 8, 33-41 3. Hoffman, M. D., Sniatynski, M. J., Rogalski, J. C., Le Blanc, J. C., and Kast, J. (2006) Multiple neutral loss monitoring (MNM): a multiplexed method for post-translational modification screening. J Am Soc Mass Spectrom 17, 307-317 4. Cain, J. A., Solis, N., and Cordwell, S. J. (2014) Beyond gene expression: the impact of protein post-translational modifications in bacteria. J Proteomics 97, 265-286 5. Soppa, J. (2010) Protein acetylation in archaea, bacteria, and eukaryotes. Archaea 2010 6. Jones, J. D., and O'Connor, C. D. (2011) Protein acetylation in prokaryotes. Proteomics 11, 3012-3022 7. Hu, L. I., Lima, B. P., and Wolfe, A. J. (2010) Bacterial protein acetylation: the dawning of a new age. Mol Microbiol 77, 15-21 8. Phillips, D. M. (1963) The presence of acetyl groups of histones. Biochem J 87, 258-263 9. Kim, S. C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., Grishin, N. V., White, M., Yang, X. J., and Zhao, Y. (2006) Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23, 607-618 10. Yang, X. J. (2004) The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res 32, 959-976 11. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M. L., Rehman, M., Walther, T. C., Olsen, J. V., and Mann, M. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325, 834-840 12. Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Xie, L., Zhao, W., Yao, Y., Ning, Z. B., Zeng, R., Xiong, Y., Guan, K. L., Zhao, S., and Zhao, G. P. (2010) Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 327, 1004-1007 13. Lee, J. V., Carrer, A., Shah, S., Snyder, N. W., Wei, S., Venneti, S., Worth, A. J., Yuan, Z. F., Lim, H. W., Liu, S., Jackson, E., Aiello, N. M., Haas, N. B., Rebbeck, T. R., Judkins, A., Won, K. J., Chodosh, L. A., Garcia, B. A., Stanger, B. Z., Feldman, M. D., Blair, I. A., and Wellen, K. E. (2014) Akt-dependent metabolic reprogramming regulates tumor cell histone acetylation. Cell Metab 20, 306-319 14. Nambi, S., Gupta, K., Bhattacharyya, M., Ramakrishnan, P., Ravikumar, V., Siddiqui, N., Thomas, A. T., and Visweswariah, S. S. (2013) Cyclic AMP-dependent protein lysine acylation in mycobacteria regulates fatty acid and propionate metabolism. J Biol Chem 288, 14114-14124 15. Guan, K. L., and Xiong, Y. (2011) Regulation of intermediary metabolism by protein acetylation. Trends Biochem Sci 36, 108-116 16. Overmyer, K. A., Evans, C. R., Qi, N. R., Minogue, C. E., Carson, J. J., Chermside-Scabbo, C. J., Koch, L. G., Britton, S. L., Pagliarini, D. J., Coon, J. J., and Burant, C. F. (2015) Maximal Oxidative Capacity during Exercise Is Associated with Skeletal Muscle Fuel Selection and Dynamic Changes in Mitochondrial Protein Acetylation. Cell Metab 21, 468-478 17. Tang, J., Cho, N. W., Cui, G., Manion, E. M., Shanbhag, N. M., Botuyan, M. V., Mer, G., and Greenberg, R. A. (2013) Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination. Nat Struct Mol Biol 20, 317-325 18. Haigis, M. C., and Guarente, L. P. (2006) Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction. Genes Dev 20, 2913-2921 19. Blander, G., and Guarente, L. (2004) The Sir2 family of protein deacetylases. Annu Rev Biochem 73, 417-435 20. McKinsey, T. A., and Olson, E. N. (2004) Cardiac histone acetylation--therapeutic opportunities abound. Trends Genet 20, 206-213 21. Hake, S. B., Xiao, A., and Allis, C. D. (2004) Linking the epigenetic 'language' of covalent histone modifications to cancer. Br J Cancer 90, 761-769 22. Bougdour, A., Maubon, D., Baldacci, P., Ortet, P., Bastien, O., Bouillon, A., Barale, J. C., Pelloux, H., Menard, R., and Hakimi, M. A. (2009) Drug inhibition of HDAC3 and epigenetic control of differentiation in Apicomplexa parasites. J Exp Med 206, 953-966 23. Miao, J., Lawrence, M., Jeffers, V., Zhao, F., Parker, D., Ge, Y., Sullivan, W. J., Jr., and Cui, L. (2013) Extensive lysine acetylation occurs in evolutionarily conserved metabolic pathways and parasite-specific functions during Plasmodium falciparum intraerythrocytic development. Mol Microbiol 89, 660-675 24. Filippakopoulos, P., and Knapp, S. (2014) Targeting bromodomains: epigenetic readers of lysine acetylation. Nat Rev Drug Discov 13, 337-356 25. Yu, B. J., Kim, J. A., Moon, J. H., Ryu, S. E., and Pan, J. G. (2008) The diversity of lysine-acetylated proteins in Escherichia coli. J Microbiol Biotechnol 18, 1529-1536 26. Zhang, J., Sprung, R., Pei, J., Tan, X., Kim, S., Zhu, H., Liu, C. F., Grishin, N. V., and Zhao, Y. (2009) Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli. Mol Cell Proteomics 8, 215-225 27. Zhang, K., Zheng, S., Yang, J. S., Chen, Y., and Cheng, Z. (2013) Comprehensive profiling of protein lysine acetylation in Escherichia coli. J Proteome Res 12, 844-851 28. Okanishi, H., Kim, K., Masui, R., and Kuramitsu, S. (2013) Acetylome with structural mapping reveals the significance of lysine acetylation in Thermus thermophilus. J Proteome Res 12, 3952-3968 29. Kim, D., Yu, B. J., Kim, J. A., Lee, Y. J., Choi, S. G., Kang, S., and Pan, J. G. (2013) The acetylproteome of Gram-positive model bacterium Bacillus subtilis. Proteomics 13, 1726-1736 30. Pan, J., Ye, Z., Cheng, Z., Peng, X., Wen, L., and Zhao, F. (2014) Systematic analysis of the lysine acetylome in Vibrio parahemolyticus. J Proteome Res 13, 3294-3302 31. Liu, F., Yang, M., Wang, X., Yang, S., Gu, J., Zhou, J., Zhang, X. E., Deng, J., and Ge, F. (2014) Acetylome analysis reveals diverse functions of lysine acetylation in Mycobacterium tuberculosis. Mol Cell Proteomics 13, 3352-3366 32. Xie, L., Wang, X., Zeng, J., Zhou, M., Duan, X., Li, Q., Zhang, Z., Luo, H., Pang, L., Li, W., Liao, G., Yu, X., Li, Y., Huang, H., and Xie, J. (2015) Proteome-wide lysine acetylation profiling of the human pathogen Mycobacterium tuberculosis. Int J Biochem Cell Biol 59, 193-202 33. Wu, X., Vellaichamy, A., Wang, D., Zamdborg, L., Kelleher, N. L., Huber, S. C., and Zhao, Y. (2013) Differential lysine acetylation profiles of Erwinia amylovora strains revealed by proteomics. J Proteomics 79, 60-71 34. Lee, D. W., Kim, D., Lee, Y. J., Kim, J. A., Choi, J. Y., Kang, S., and Pan, J. G. (2013) Proteomic analysis of acetylation in thermophilic Geobacillus kaustophilus. Proteomics 13, 2278-2282 35. Liao, G., Xie, L., Li, X., Cheng, Z., and Xie, J. (2014) Unexpected extensive lysine acetylation in the trump-card antibiotic producer Streptomyces roseosporus revealed by proteome-wide profiling. J Proteomics 106, 260-269 36. Chen, Y., Sprung, R., Tang, Y., Ball, H., Sangras, B., Kim, S. C., Falck, J. R., Peng, J., Gu, W., and Zhao, Y. (2007) Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol Cell Proteomics 6, 812-819 37. Cheng, Z., Tang, Y., Chen, Y., Kim, S., Liu, H., Li, S. S., Gu, W., and Zhao, Y. (2009) Molecular characterization of propionyllysines in non-histone proteins. Mol Cell Proteomics 8, 45-52 38. Liu, B., Lin, Y., Darwanto, A., Song, X., Xu, G., and Zhang, K. (2009) Identification and characterization of propionylation at histone H3 lysine 23 in mammalian cells. J Biol Chem 284, 32288-32295 39. Fritz, K. S., Green, M. F., Petersen, D. R., and Hirschey, M. D. (2013) Ethanol metabolism modifies hepatic protein acylation in mice. PLoS One 8, e75868 40. Okanishi, H., Kim, K., Masui, R., and Kuramitsu, S. (2014) Lysine propionylation is a prevalent post-translational modification in Thermus thermophilus. Mol Cell Proteomics 13, 2382-2398 41. Zhao, Y., and Jensen, O. N. (2009) Modification-specific proteomics: strategies for characterization of post-translational modifications using enrichment techniques. Proteomics 9, 4632-4641 42. Han, X., Aslanian, A., and Yates, J. R., 3rd (2008) Mass spectrometry for proteomics. Curr Opin Chem Biol 12, 483-490 43. Chen, Y., Kwon, S. W., Kim, S. C., and Zhao, Y. (2005) Integrated approach for manual evaluation of peptides identified by searching protein sequence databases with tandem mass spectra. J Proteome Res 4, 998-1005 44. Liu, Z., Wang, Y., Gao, T., Pan, Z., Cheng, H., Yang, Q., Cheng, Z., Guo, A., Ren, J., and Xue, Y. (2014) CPLM: a database of protein lysine modifications. Nucleic Acids Res 42, D531-536 45. Lu, C. T., Huang, K. Y., Su, M. G., Lee, T. Y., Bretana, N. A., Chang, W. C., Chen, Y. J., Chen, Y. J., and Huang, H. D. (2013) DbPTM 3.0: an informative resource for investigating substrate site specificity and functional association of protein post-translational modifications. Nucleic Acids Res 41, D295-305 46. Li, H., Xing, X., Ding, G., Li, Q., Wang, C., Xie, L., Zeng, R., and Li, Y. (2009) SysPTM: a systematic resource for proteomic research on post-translational modifications. Mol Cell Proteomics 8, 1839-1849 47. Webster, C., Towner, K. J., and Humphreys, H. (2000) Survival of Acinetobacter on three clinically related inanimate surfaces. Infect Control Hosp Epidemiol 21, 246 48. Lee, N. Y., Lee, H. C., Ko, N. Y., Chang, C. M., Shih, H. I., Wu, C. J., and Ko, W. C. (2007) Clinical and economic impact of multidrug resistance in nosocomial Acinetobacter baumannii bacteremia. Infect Control Hosp Epidemiol 28, 713-719 49. Wisplinghoff, H., Bischoff, T., Tallent, S. M., Seifert, H., Wenzel, R. P., and Edmond, M. B. (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39, 309-317 50. Garnacho-Montero, J., Ortiz-Leyba, C., Fernandez-Hinojosa, E., Aldabo-Pallas, T., Cayuela, A., Marquez-Vacaro, J. A., Garcia-Curiel, A., and Jimenez-Jimenez, F. J. (2005) Acinetobacter baumannii ventilator-associated pneumonia: epidemiological and clinical findings. Intensive Care Med 31, 649-655 51. Metan, G., Alp, E., Aygen, B., and Sumerkan, B. (2007) Acinetobacter baumannii meningitis in post-neurosurgical patients: clinical outcome and impact of carbapenem resistance. J Antimicrob Chemother 60, 197-199 52. Wendt, C., Dietze, B., Dietz, E., and Ruden, H. (1997) Survival of Acinetobacter baumannii on dry surfaces. J Clin Microbiol 35, 1394-1397 53. Smith, M. G., Gianoulis, T. A., Pukatzki, S., Mekalanos, J. J., Ornston, L. N., Gerstein, M., and Snyder, M. (2007) New insights into Acinetobacter baumannii pathogenesis revealed by high-density pyrosequencing and transposon mutagenesis. Genes Dev 21, 601-614 54. Adams, M. D., Goglin, K., Molyneaux, N., Hujer, K. M., Lavender, H., Jamison, J. J., MacDonald, I. J., Martin, K. M., Russo, T., Campagnari, A. A., Hujer, A. M., Bonomo, R. A., and Gill, S. R. (2008) Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii. J Bacteriol 190, 8053-8064 55. Su, C. H., Wang, J. T., Hsiung, C. A., Chien, L. J., Chi, C. L., Yu, H. T., Chang, F. Y., and Chang, S. C. (2012) Increase of carbapenem-resistant Acinetobacter baumannii infection in acute care hospitals in Taiwan: association with hospital antimicrobial usage. PLoS One 7, e37788 56. Zavascki, A. P., Goldani, L. Z., Li, J., and Nation, R. L. (2007) Polymyxin B for the treatment of multidrug-resistant pathogens: a critical review. J Antimicrob Chemother 60, 1206-1215 57. Tang, S. S., Apisarnthanarak, A., and Hsu, L. Y. (2014) Mechanisms of beta-lactam antimicrobial resistance and epidemiology of major community- and healthcare-associated multidrug-resistant bacteria. Adv Drug Deliv Rev 78, 3-13 58. Ploy, M. C., Giamarellou, H., Bourlioux, P., Courvalin, P., and Lambert, T. (1994) Detection of aac(6')-I genes in amikacin-resistant Acinetobacter spp. by PCR. Antimicrob Agents Chemother 38, 2925-2928 59. Shaw, K. J., Rather, P. N., Hare, R. S., and Miller, G. H. (1993) Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes. Microbiol Rev 57, 138-163 60. Chen, T. L., Lee, Y. T., Kuo, S. C., Hsueh, P. R., Chang, F. Y., Siu, L. K., Ko, W. C., and Fung, C. P. (2010) Emergence and Distribution of Plasmids Bearing the blaOXA-51-like gene with an upstream ISAba1 in carbapenem-resistant Acinetobacter baumannii isolates in Taiwan. Antimicrob Agents Chemother 54, 4575-4581 61. Lee, Y. T., Kuo, S. C., Chiang, M. C., Yang, S. P., Chen, C. P., Chen, T. L., and Fung, C. P. (2012) Emergence of carbapenem-resistant non-baumannii species of Acinetobacter harboring a blaOXA-51-like gene that is intrinsic to A. baumannii. Antimicrob Agents Chemother 56, 1124-1127 62. Aziz, R. K., Bartels, D., Best, A. A., DeJongh, M., Disz, T., Edwards, R. A., Formsma, K., Gerdes, S., Glass, E. M., Kubal, M., Meyer, F., Olsen, G. J., Olson, R., Osterman, A. L., Overbeek, R. A., McNeil, L. K., Paarmann, D., Paczian, T., Parrello, B., Pusch, G. D., Reich, C., Stevens, R., Vassieva, O., Vonstein, V., Wilke, A., and Zagnitko, O. (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9, 75 63. Yu, N. Y., Wagner, J. R., Laird, M. R., Melli, G., Rey, S., Lo, R., Dao, P., Sahinalp, S. C., Ester, M., Foster, L. J., and Brinkman, F. S. (2010) PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26, 1608-1615 64. Yang, J., Yan, R., Roy, A., Xu, D., Poisson, J., and Zhang, Y. (2015) The I-TASSER Suite: protein structure and function prediction. Nat Methods 12, 7-8 65. Roy, A., Kucukural, A., and Zhang, Y. (2010) I-TASSER: a unified platform for automated protein structure and function prediction. Nature protocols 5, 725-738 66. Zhang, Y. (2008) I-TASSER server for protein 3D structure prediction. BMC Bioinformatics 9, 40 67. Chan, J. W., and Goodwin, P. H. (1995) Extraction of genomic DNA from extracellular polysaccharide-synthesizing gram-negative bacteria. Biotechniques 18, 418-422 68. Chiu, J., March, P. E., Lee, R., and Tillett, D. (2004) Site-directed, Ligase-Independent Mutagenesis (SLIM): a single-tube methodology approaching 100% efficiency in 4 h. Nucleic Acids Res 32, e174 69. Schagger, H., and von Jagow, G. (1991) Blue native electrophoresis for isolation of membrane protein complexes in enzymatically active form. Anal Biochem 199, 223-231 70. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., Li, Y., Shi, J., An, W., Hancock, S. M., He, F., Qin, L., Chin, J., Yang, P., Chen, X., Lei, Q., Xiong, Y., and Guan, K. L. (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-1004 71. Weinert, B. T., Wagner, S. A., Horn, H., Henriksen, P., Liu, W. R., Olsen, J. V., Jensen, L. J., and Choudhary, C. (2011) Proteome-wide mapping of the Drosophila acetylome demonstrates a high degree of conservation of lysine acetylation. Sci Signal 4, ra48 72. Finkemeier, I., Laxa, M., Miguet, L., Howden, A. J., and Sweetlove, L. J. (2011) Proteins of diverse function and subcellular location are lysine acetylated in Arabidopsis. Plant Physiol 155, 1779-1790 73. Yang, L., Vaitheesvaran, B., Hartil, K., Robinson, A. J., Hoopmann, M. R., Eng, J. K., Kurland, I. J., and Bruce, J. E. (2011) The fasted/fed mouse metabolic acetylome: N6-acetylation differences suggest acetylation coordinates organ-specific fuel switching. J Proteome Res 10, 4134-4149 74. Spange, S., Wagner, T., Heinzel, T., and Kramer, O. H. (2009) Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol 41, 185-198 75. Kovacs, J. J., Murphy, P. J., Gaillard, S., Zhao, X., Wu, J. T., Nicchitta, C. V., Yoshida, M., Toft, D. O., Pratt, W. B., and Yao, T. P. (2005) HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 18, 601-607 76. Scroggins, B. T., Robzyk, K., Wang, D., Marcu, M. G., Tsutsumi, S., Beebe, K., Cotter, R. J., Felts, S., Toft, D., Karnitz, L., Rosen, N., and Neckers, L. (2007) An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 25, 151-159 77. Drlica, K., and Rouviere-Yaniv, J. (1987) Histonelike proteins of bacteria. Microbiol Rev 51, 301-319 78. Swinger, K. K., Lemberg, K. M., Zhang, Y., and Rice, P. A. (2003) Flexible DNA bending in HU-DNA cocrystal structures. EMBO J 22, 3749-3760 79. Fujimoto, H., Higuchi, M., Koike, M., Ode, H., Pinak, M., Bunta, J. K., Nemoto, T., Sakudoh, T., Honda, N., Maekawa, H., Saito, K., and Tsuchida, K. (2012) A possible overestimation of the effect of acetylation on lysine residues in KQ mutant analysis. J Comput Chem 33, 239-246 80. Goshima, N., Kohno, K., Imamoto, F., and Kano, Y. (1990) HU-1 mutants of Escherichia coli deficient in DNA binding. Gene 96, 141-145 81. Broyles, S. S., and Pettijohn, D. E. (1986) Interaction of the Escherichia coli HU protein with DNA. Evidence for formation of nucleosome-like structures with altered DNA helical pitch. J Mol Biol 187, 47-60 82. Kar, S., Edgar, R., and Adhya, S. (2005) Nucleoid remodeling by an altered HU protein: reorganization of the transcription program. Proc Natl Acad Sci U S A 102, 16397-16402 83. Bhowmick, T., Ghosh, S., Dixit, K., Ganesan, V., Ramagopal, U. A., Dey, D., Sarma, S. P., Ramakumar, S., and Nagaraja, V. (2014) Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors. Nat Commun 5, 4124 84. Reiff, S. B., Vaishnava, S., and Striepen, B. (2012) The HU protein is important for apicoplast genome maintenance and inheritance in Toxoplasma gondii. Eukaryot Cell 11, 905-915 85. Mangan, M. W., Lucchini, S., T, O. C., Fitzgerald, S., Hinton, J. C., and Dorman, C. J. (2011) Nucleoid-associated protein HU controls three regulons that coordinate virulence, response to stress and general physiology in Salmonella enterica serovar Typhimurium. Microbiology 157, 1075-1087 86. McGhee, J.D. and Felsenfeld, G. (1980) Nucleosome structure. Annu Rev Biochem, 49, 1115-1156. 87. Thanbichler, M., Wang, S.C. and Shapiro, L. (2005) The bacterial nucleoid: a highly organized and dynamic structure. J Cell Biochem, 96, 506-521. 88. Grove, A. (2011) Functional evolution of bacterial histone-like HU proteins. Curr. Issues Mol. Biol., 13, 1-12. 89. Oberto, J., Nabti, S., Jooste, V., Mignot, H. and Rouviere-Yaniv, J. (2009) The HU regulon is composed of genes responding to anaerobiosis, acid stress, high osmolarity and SOS induction. PLoS One, 4, e4367. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/17774 | - |
| dc.description.abstract | 離胺酸乙醯化是一種廣泛分布於真核生物和細菌中的蛋白質轉譯後修飾。近來的研究發現，在真核生物中，許多乙醯化蛋白質於細胞各式各樣的反應中扮演著舉足輕重的角色，然而在原核細胞內，蛋白質乙醯化的功能和遍布範圍仍不明瞭。另外，離胺酸丙醯化是一個近年來新發現的離胺酸修飾，它被認為也對調控生物體的生理反應有著深遠的影響。本篇研究以質譜儀技術為基礎，並結合抗體免疫沉澱法進行蛋白質體學之分析，於醫院臨床菌株鮑氏不動桿菌SK17(Acinetobacter baumannii SK17)中檢測到174個乙醯化修飾位及96個丙醯化修飾位，分別來自於菌體中128個乙醯化蛋白質和71個丙醯化蛋白質。將這些乙醯化與丙醯化蛋白質體利用生物資訊學加以剖析後，我們發現這些蛋白質參與在多種不同的細胞反應中，包括核苷酸代謝、胺基酸代謝、醣類代謝、膜上運輸以及壓力反應。為了進一步確認這些轉譯後修飾對於蛋白質的影響，我們利用同源結構模擬法進行更深入的探討。當中有一個名為DNA結合蛋白HU (DNA-binding protein HU or nucleoid-associated protein HU)的二元體蛋白質，已知為染色體構型的維持和各種DNA相關反應的調節中重要的一員。此蛋白胺基酸序列第十三號的離胺酸上被偵測到有乙醯化的修飾，並且我們更驗證了這個修飾反應會改變HU蛋白的四級結構，以及降低其DNA的結合能力。本篇證實離胺酸乙醯化和丙醯化廣泛存在於鮑氏不動桿菌SK17，且建立了一個實證這些離胺酸轉譯後修飾對於生化功能的影響之成功範本，供後續研究的進行。 | zh_TW |
| dc.description.abstract | Lysine acetylation is one of the most prevalent post-translational modifications (PTMs) detected in both eukaryotes and bacteria. Recently, many acetylproteins have been reported to play pivotal roles in various cellular processes in eukaryotes. However, the function and extent of this modification in prokaryotic cells remain largely unexplored. Besides, another novel lysine modification, lysine propionylation, is potential to have important functions in the regulation of biological processes. In this study, by using a mass spectrometry-based proteomic approach in combination with immunoprecipitation, we identified 174/ 96 lysine acetylation/ propionylation sites from 128/ 71 acetyl-/ propionylproteins in clinical isolates of Acinetobacter baumannii SK17. The bioinformatics analysis of both acetylome and propionylome showed that the identified proteins were involved in diverse cellular functions including nucleotide metabolism, amino acid metabolism, carbohydrate metabolism, membrane transporter and stress response. To further characterize the definite effects of these PTMs on proteins, we examined the identification of lysine-modified peptides based on their homologous protein structures. Among these, DNA-binding protein HU (also known as nucleoid-associated protein HU), a small dimeric protein, playing a critical role in maintenance of chromosomal architecture and various DNA transactions, was acetylated on Lys-13. In addition, we further proved this acetylated site would influence the stability of quaternary structure of HU protein and decrease its DNA binding ability. Our findings demonstrated that lysine acetylation and propinylation are abundant in A. baumannii SK17 and provide an in-depth exploration of the biological functions on lysine acetylated and propionylated proteins. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T00:43:20Z (GMT). No. of bitstreams: 1 ntu-104-R02b46024-1.pdf: 15040307 bytes, checksum: 3a4cce89012d1a0a0ed3f615c6669f0c (MD5) Previous issue date: 2015 | en |
| dc.description.tableofcontents | 謝誌 i
摘要 iii Abstract iv Table of Contents vi List of Figures ix List of Tables xi Abbreviation Table xii Chapter 1 Introduction 1 1-1 A brief overview: From post-translational modification to lysine acetylation 1 1-2 Protein acetylation in bacteria 2 1-3 The current development of lysine propionylation 3 1-4 Mass spectrometry (MS)-based acetylome and propionylome 4 1-5 The feature of multidrug-resistant Acinetobacter baumannii 5 1-6 Nucleoid-associated protein HU 7 1-7 Aim of this study 8 Chapter 2 Material and Method 9 2-1 Bacterial strains growth conditions and protein extraction 9 2-2 In-solution protein digestion and acetylpeptide/propionylpeptide enrichment 10 2-3 NanoLC-MS/MS analysis 12 2-4 Data processing and validation 13 2-5 Bioinformatics analysis 14 2-6 Homology modeling 15 2-7 Construction of HU-beta expression plasmids and site-directed mutagenesis 16 2-8 Expression and purification of HU-beta and mutant protein 16 2-9 Native polyacrylamide gel electrophoresis (Native-PAGE) 18 2-10 Analytical ultracentrifugation (AUC) 18 2-11 Electrophoretic mobility shift assay (EMSA) 19 2-12 Circular dichroism (CD) spectra 20 Chapter 3 Result 21 3-1 Acetylome of A. baumannii SK17R and SK17S 21 3-2 Propionylome of A. baumannii SK17R and SK17S 25 3-3 Classification of the identified acetylproteins 28 3-4 Classification of the identified propionylproteins 32 3-5 Structural mapping indicates the significance of lysine acetylation of DNA-binding protein HU 35 3-6 Sedimentation patterns and Tm values reveal the conformation difference between WT and acetyl-mimetic K to Q mutant AbHU 40 3-7 The KQ mutant of AbHU affects its DNA-binding ability 46 Chapter 4 Conclusion and Discussion 48 4-1 The global profiles of acetylome and propionylome in Acinetobacter baumannii SK17-R and SK17-S 48 4-2 Proteomics approaches in combination with structural mappings provide a potential way for in-depth explorations of PTMs 49 4-3 A prospective treatment for A. baumannii: setting off from AbHU on the basis of lysine acetylation 53 Reference 57 Appendix 65 Appendix 1. The detailed list of the identified acetylproteins in A. baumannii SK17. 65 Appendix 2. Information of cellular localization and putative function of acetylproteins in A. baumannii SK17. 70 Appendix 3. The detailed list of the identified propionylproteins in A. baumannii SK17-R and SK17-S 75 Appendix 4. Information of cellular localization and putative function of propionylproteins in A. baumannii SK17. 78 Appendix 5. SDS-PAGE and Native-PAGE of purified AbHU 81 Appendix 6. Primers, plasmids, and PCR programs applied in this study. 82 | |
| dc.language.iso | en | |
| dc.title | 鮑氏不動桿菌SK17乙醯化及丙醯化蛋白質體之研究 | zh_TW |
| dc.title | Acetylome and propionylome of Acinetobacter baumannii SK17 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 梁博煌(Po-Huang Liang),花國鋒(Kuo-Feng Hua),黃人則(Jen-Tse Huang) | |
| dc.subject.keyword | 離氨酸乙醯化,離氨酸丙醯化,鮑氏不動桿菌SK17,DNA結合蛋白HU-β, | zh_TW |
| dc.subject.keyword | lysine acetylation,lysine propionylation,A. baumannii SK17,DNA-binding protein HU-β, | en |
| dc.relation.page | 83 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2015-08-13 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-104-1.pdf 未授權公開取用 | 14.69 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。