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研究生:羅際偉
研究生(外文):Chi-Wei Lo
論文名稱:介白素8類似物的骨架動態行為研究
論文名稱(外文):Backbone dynamics of an IL-8 analogue
指導教授:程家維
指導教授(外文):Jya-Wei Cheng
學位類別:碩士
校院名稱:國立清華大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2007
畢業學年度:95
語文別:英文
論文頁數:53
中文關鍵詞:骨架動態介白素8
外文關鍵詞:backbone dynamicsinterleukin-8
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趨化激素在人類病理學中嗜中性白血球相關的發炎反應中扮演重要的角色。 ELR-CXC趨化激素屬於趨化激素中的CXC子集且N端具有ELR功能區。 ELR-CXC 間白素因為他們對於嗜中性白血球的趨化性及活化性而在致病性的發炎反應中扮演重要的腳色。 這個有兩個突變位置 (K11R/G31P) 的CXCL8類似物可有效的透過CXCR1跟CXCR2阻斷嗜中性白血球對於發炎的反應。 我們測量了14.1T磁場下的自旋-晶格遲緩速率R1、自旋-自旋遲緩速率R2及15N {H}異核交互作用增益參數(NOE)。 利用程式pdbinteria及R2R1_diffusion來預測擴散張量(diffusion tensor)。 之後, 利用無模型法則(Model-free formalism)決定次序參數(S2)、有效相關時間(τe)及化學交換參數(Rex)。 對應不同頻率的簡化光譜密度方程式(reduced spectral density functions)也用來提供遲緩運動的資訊。 這些分析可提供IL8K11R/G31P骨架動態的相關資訊, 得知Arg11跟Pro31附近的區域會比其他區域更具活動性。
Chemkines play an important role in the neutrophil-mediated inflammation in human pathophysiology. ELR-CXC chemkines belong to the CXC subfamily of chemkines with ELR-motif at the N-terminal region. The ELR-CXC chemokines play an important role in inflammatory responses to many pathogenic insults as their ability to chemoattract and activate neutrophils via CXC receptor.
The analogue of CXCL8 (IL-8) in which two residues were mutated (IL8K11R/G31P) can effectively block neutrophil responses via CXCR1 and CXCR2. We measured the spin-lattice relaxation rate R1, spin-spin relaxation rate R2 and 15N {H} nuclear overhauser enhancement (NOE) of IL8K11R/G31P at 14.09T. The programs pdbinteria and R2R1_diffusion were used to estimate the diffusion tensor and generate a new pdb file. Then, Model-free formalism was performed to determine the order parameter (S2), the correlation time of local motion (τe) and the chemical exchange contribution (Rex). The reduced spectral density functions at different frequencies were also used to obtain the relaxation information.
These analysis provided information that backbone dynamics of IL8K11R/G31P around Arg11 and Pro31 are more flexible than other region.
誌謝 I
摘要 III
Abstract IV
Chapter 1
Introduction 1
1.2 Structure-function relationship of Interleukin 8 2
1.3 The antagonist of interleukin-8; the analogue of interleukin-8 with two mutated positions 3
Chapter 2
NMR relaxation theory for protein dynamics 5
2.1 Protein dynamics monitor by NMR relaxation 5
2.2 NMR relaxation aspects 6
2.3 Relaxation Parameters- R1, R2 and NOE 6
2.3 Model-free Formalism 8
2.4 Model definition and application 10
2.5 Model selection 12
2.6 Model-free analysis with FASTmodelfree interface 14
2.7 Reduce Spectral Density Mapping 17
Chapter 3
Materials and Methods 20
3.1. Protein Sample Preparation 20
3.1.2 Protein Expression and Purification 20
3.13 Relaxation Data Acquisition and Process 21
Chapter 4
Result…….. 23
4.1 Relaxation parameters- R1, R2 and NOE 23
4.2 Reduced Spectral Density Mapping 25
4.3 Rotational Diffusion Tensor Estimate 25
4.5 Model-free analysis 27
Chapter 5
Discussion. 29
5.1 Relaxation properties revealed in this study 29
5.2 Relaxation differences in the proposed binding areas 32
5.3 Self-criticisms and future directions 33
Reference… ..52
1. Anthony, D., Dempster, R., Fearn, S., Clements, J., Wells, G., Perry, V. H., and Walker, K. (1998) Curr Biol 8(16), 923-926
2. Harlan, J. M. (1987) Acta Med Scand Suppl 715, 123-129
3. Jaeschke, H., and Hasegawa, T. (2006) Liver Int 26(8), 912-919
4. Yoshida, N., Yoshikawa, T., Nakamura, Y., Arai, M., Matsuyama, K., Iinuma, S., Yagi, N., Naito, Y., Miyasaka, M., and Kondo, M. (1995) Dig Dis Sci 40(11), 2300-2304
5. Baggiolini, M., Loetscher, P., and Moser, B. (1995) Int J Immunopharmacol 17(2), 103-108
6. Gillitzer, R., and Goebeler, M. (2001) J Leukoc Biol 69(4), 513-521
7. Strieter, R. M., Polverini, P. J., Kunkel, S. L., Arenberg, D. A., Burdick, M. D., Kasper, J., Dzuiba, J., Van Damme, J., Walz, A., Marriott, D., and et al. (1995) J Biol Chem 270(45), 27348-27357
8. Clark-Lewis, I., Dewald, B., Geiser, T., Moser, B., and Baggiolini, M. (1993) Proc Natl Acad Sci U S A 90(8), 3574-3577
9. Clark-Lewis, I., Schumacher, C., Baggiolini, M., and Moser, B. (1991) J Biol Chem 266(34), 23128-23134
10. Hebert, C. A., Vitangcol, R. V., and Baker, J. B. (1991) J Biol Chem 266(28), 18989-18994
11. Lindley, I., Aschauer, H., Seifert, J. M., Lam, C., Brunowsky, W., Kownatzki, E., Thelen, M., Peveri, P., Dewald, B., von Tscharner, V., and et al. (1988) Proc Natl Acad Sci U S A 85(23), 9199-9203
12. Clore, G. M., Appella, E., Yamada, M., Matsushima, K., and Gronenborn, A. M. (1990) Biochemistry 29(7), 1689-1696
13. Baldwin, E. T., Weber, I. T., St Charles, R., Xuan, J. C., Appella, E., Yamada, M., Matsushima, K., Edwards, B. F., Clore, G. M., Gronenborn, A. M., and et al. (1991) Proc Natl Acad Sci U S A 88(2), 502-506
14. Hammond, M. E., Shyamala, V., Siani, M. A., Gallegos, C. A., Feucht, P. H., Abbott, J., Lapointe, G. R., Moghadam, M., Khoja, H., Zakel, J., and Tekamp-Olson, P. (1996) J Biol Chem 271(14), 8228-8235
15. Clark-Lewis, I., Dewald, B., Loetscher, M., Moser, B., and Baggiolini, M. (1994) J Biol Chem 269(23), 16075-16081
16. Skelton, N. J., Quan, C., Reilly, D., and Lowman, H. (1999) Structure 7(2), 157-168
17. Gordon, J. R., Li, F., Zhang, X., Wang, W., Zhao, X., and Nayyar, A. (2005) J Leukoc Biol 78(6), 1265-1272
18. Li, F., and Gordon, J. R. (2001) Biochem Biophys Res Commun 286(3), 595-600
19. Li, F., Zhang, X., and Gordon, J. R. (2002) Biochem Biophys Res Commun 293(3), 939-944
20. Li, F., Zhang, X., Mizzi, C., and Gordon, J. R. (2002) Vet Immunol Immunopathol 90(1-2), 65-77
21. Clore, G. M., Driscoll, P. C., Wingfield, P. T., and Gronenborn, A. M. (1990) Biochemistry 29(32), 7387-7401
22. Farrow, N. A., Zhang, O., Szabo, A., Torchia, D. A., and Kay, L. E. (1995) J Biomol NMR 6(2), 153-162
23. Ishima, R., and Nagayama, K. (1995) Biochemistry 34(10), 3162-3171
24. Nicholson, L. K., Kay, L. E., Baldisseri, D. M., Arango, J., Young, P. E., Bax, A., and Torchia, D. A. (1992) Biochemistry 31(23), 5253-5263
25. Grasberger, B. L., Gronenborn, A. M., and Clore, G. M. (1993) J Mol Biol 230(2), 364-372
26. Huang, Y. T., Liaw, Y. C., Gorbatyuk, V. Y., and Huang, T. H. (2001) J Mol Biol 307(4), 1075-1090
27. Peng, J. W., and Wagner, G. (1992) Biochemistry 31(36), 8571-8586
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