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研究生:姚永霖
研究生(外文):Yong-Lin Yao
論文名稱(外文):Sliding of Sso7c4 Protein on DNA Backbone Investigated by Molecular Dynamic Simulations
指導教授:蔡惠旭
指導教授(外文):Hui-Hsu Gavin Tsai
學位類別:碩士
校院名稱:國立中央大學
系所名稱:化學學系
學門:自然科學學門
學類:化學學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:74
中文關鍵詞:硫化葉菌DNA結合蛋白DNA彎曲
外文關鍵詞:SulfolobusSso7c4DNA binding proteinDNA bending
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硫磺礦硫化葉菌(Sulfolobus solfataricus)擁有耐熱抗性以及耐酸抗性,在攝氏溫度80-85度和酸鹼值2-4的時候生長最為優良,所以硫磺礦硫化葉菌可以在火山和溫泉等地找到。硫磺礦硫化葉菌擁有分子量7kDa、8kDa以及10kDa的去氧核糖核酸結合蛋白質,其中,本篇論文中所使用的Sso7c4正是屬於7kDa裡的其中一個。Sso7c4是一種類組織蛋白(histone-like)的蛋白質二聚體,同樣地,Sso7c4也擁有耐熱抗性以及耐酸抗性。
在本篇論文中,我們建構了一個初始模型,包含了兩個Sso7c4二聚體蛋白質和長度為24個鹼基的雙股去氧核醣核酸,並且我們採用了分子動態模擬來模擬這個系統,研究Sso7c4二聚體蛋白質和去氧核醣核酸之間的交互作用。
在模擬中,我們觀察到,Sso7c4裡的精胺酸(R22/R11′)以及羧基端(C-terminus)都會和去氧核醣核酸的骨架上的磷酸鹽有交互作用,這個觀察結果跟先前的研究結果相符合。除此之外,我們還發現到,除了精胺酸(R22/R11′)以及羧基端之外,Sso7c4裡的帶正電荷的離胺酸(K)也會和去氧核醣核酸的骨架上的磷酸鹽有交互作用,有趣的是,離胺酸在Sso7c4蛋白質序列裡佔了8個(K8,K20,K24,K28,K34,K45,K50,K54),有6個(K8,K20,K24,K28,K50,K54)有交互作用。
接觸圖(contact map)的分析顯示了兩個Sso7c4蛋白質二聚體之間有重要的分子間作用。特別的是,我們還觀察到了Sso7c4蛋白質二聚體在去氧核醣核酸的骨架上的移動(slide),正是這些交互作用使去氧核醣核酸結構變形、彎曲。
Sulfolobus solfataricus can be found in volcanoes and hot spring. It grows best at 80-85°C and at the pH level of 2-4. Sso7c4, a member of 7-kDa families of Sulfolobus solfataricus, is a histone-like dimer protein; it can resist to heat and acid. In this study, we employed molecular dynamics simulations to investigate the interactions between Sso7c4 dimers and a double-stranded DNA. We observed that an arginine pair (R22/R11′) and C-terminus of Sso7c4 have significant interactions with the phosphates on the DNA backbone, which are consistent with results of binding assay. In addition, we also observed that six positively charged lysine residues (K8,K20,K24,K28,K50,K54) have interactions with the phosphates on the DNA backbone. Furthermore, the whole Sso7c4 proteins sliding on DNA backbone is observed. Contact map analysis shows the two Sso7c4 dimers have important intermolecular interactions through hydrophobic residues pulling two Sso7c4 dimers closer. These interactions and the sliding of proteins on DNA backbone deform the DNA structure such as bending and shortening the DNA length.
摘要 i
Abstract ii
致謝 iii
Table of contents iv
List of Figures vi
List of Tables ix
Introduction 1
Computational Methods 4
Construction of initial Sso7c4-DNA complex Model 4
Computational details 11
Trajectory Analysis 12
Results and Discussion 13
Structural Change 13
End-to-End Distance of DNA in Complex 15
Dimer to Dimer Distance in Sso7c4-DNA complex System 19
Interactions between Sso7c4 dimers and DNA 21
Lysine-Phosphate Interactions 27
Interactions between two Sso7c4 dimers 41
Conclusion 44
References 46
Appendix A 50
Appendix B 51
Appendix C 52
Appendix D 53
Appendix E 54
Appendix F 55
Appendix G 56
Appendix H 57
Appendix I 58
Appendix J 59
Appendix K 60
References
1. Brock, T. D.; Brock, K. M.; Belly, R. T.; Weiss, R. L., Sulfolobus: A new genus of sulfur-oxidizing bacteria living at low pH and high temperature. Archiv für Mikrobiologie 1972, 84 (1), 54-68.
2. Gao, Y. G.; Su, S. Y.; Robinson, H.; Padmanabhan, S.; Lim, L.; McCrary, B. S.; Edmondson, S. P.; Shriver, J. W.; Wang, A. H. J., The crystal structure of the hyperthermophile chromosomal protein Sso7d bound to DNA. Nature Structural Biology 1998, 5 (9), 782-786.
3. Agback, P.; Baumann, H.; Knapp, S.; Ladenstein, R.; Hard, T., Architecture of nonspecific protein-DNA interactions in the Sso7d-DNA complex. Nature Structural Biology 1998, 5 (7), 579-584.
4. Forterre, P.; Confalonieri, F.; Knapp, S., Identification of the gene encoding archeal-specific DNA-binding proteins of the Sac10b family. Molecular Microbiology 1999, 32 (3), 669-670.
5. (a) Chen, L.; Chen, L.-R.; Zhou, X. E.; Wang, Y.; Kahsai, M. A.; Clark, A. T.; Edmondson, S. P.; Liu, Z.-J.; Rose, J. P.; Wang, B.-C.; Meehan, E. J.; Shriver, J. W., The Hyperthermophile Protein Sso10a is a Dimer of Winged Helix DNA-binding Domains Linked by an Antiparallel Coiled Coil Rod. Journal of Molecular Biology 2004, 341 (1), 73-91; (b) Kahsai, M. A.; Vogler, B.; Clark, A. T.; Edmondson, S. P.; Shriver, J. W., Solution structure, stability, and flexibility of Sso10a: A hyperthermophile coiled-coil DNA-binding protein. Biochemistry 2005, 44 (8), 2822-2832.
6. (a) Bell, S. D.; Botting, C. H.; Wardleworth, B. N.; Jackson, S. P.; White, M. F., The Interaction of Alba, a Conserved Archaeal Chromatin Protein, with Sir2 and Its Regulation by Acetylation. Science 2002, 296 (5565), 148-151; (b) Wardleworth, B. N.; Russell, R. J. M.; Bell, S. D.; Taylor, G. L.; White, M. F., Structure of Alba: an archaeal chromatin protein modulated by acetylation. The EMBO Journal 2002, 21 (17), 4654-4662.
7. Chou, C. C.; Lin, T. W.; Chen, C. Y.; Wang, A. H. J., Crystal structure of the hyperthermophilic archaeal DNA-binding protein Sso10b2 at a resolution of 1.85 angstroms. J. Bacteriol. 2003, 185 (14), 4066-4073.
8. (a) Vaughn, J. L.; Feher, V.; Naylor, S.; Strauch, M. A.; Cavanagh, J., Novel DNA binding domain and genetic regulation model of Bacillus subtilis transition state regulator AbrB. Nature Structural Biology 2000, 7, 1139; (b) Zorzini, V.; Buts, L.; Schrank, E.; Sterckx, Y. G. J.; Respondek, M.; Engelberg-Kulka, H.; Loris, R.; Zangger, K.; van Nuland, N. A. J., Escherichia coli antitoxin MazE as transcription factor: insights into MazE-DNA binding. Nucleic Acids Research 2015, 43 (2), 1241-1256.
9. Wu, H.-M.; Crothers, D. M., The locus of sequence-directed and protein-induced DNA bending. Nature 1984, 308, 509.
10. Dame, R. T.; van Mameren, J.; Luijsterburg, M. S.; Mysiak, M. E.; Janićijević, A.; Pazdzior, G.; van der Vliet, P. C.; Wyman, C.; Wuite, G. J. L., Analysis of scanning force microscopy images of protein-induced DNA bending using simulations. Nucleic Acids Research 2005, 33 (7), e68-e68.
11. Cam, K.; Béjar, S.; Gil, D.; Bouché, J.-P., Identification and sequence of gene dicB: translation of the division inhibitor from an in-phase internal start. Nucleic Acids Research 1988, 16 (14), 6327-6338.
12. Beck von Bodman, S.; Hayman, G. T.; Farrand, S. K., Opine catabolism and conjugal transfer of the nopaline Ti plasmid pTiC58 are coordinately regulated by a single repressor. Proceedings of the National Academy of Sciences 1992, 89 (2), 643-647.
13. Hsu, C.-H.; Wang, A. H. J., The DNA-recognition fold of Sso7c4 suggests a new member of SpoVT-AbrB superfamily from archaea. Nucleic Acids Research 2011, 39 (15), 6764-6774.
14. Lin, B.-L.; Chen, C.-Y.; Huang, C.-H.; Ko, T.-P.; Chiang, C.-H.; Lin, K.-F.; Chang, Y.-C.; Lin, P.-Y.; Tsai, H.-H. G.; Wang, A. H. J., The Arginine Pairs and C-Termini of the Sso7c4 from Sulfolobus solfataricus Participate in Binding and Bending DNA. PLOS ONE 2017, 12 (1), e0169627.
15. Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L., Comparison of simple potential functions for simulating liquid water. The Journal of chemical physics 1983, 79 (2), 926-935.
16. Case, D. A.; Cheatham, T. E.; Darden, T.; Gohlke, H.; Luo, R.; Merz, K. M.; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R. J., The Amber biomolecular simulation programs. Journal of computational chemistry 2005, 26 (16), 1668-1688.
17. Maier, J. A.; Martinez, C.; Kasavajhala, K.; Wickstrom, L.; Hauser, K. E.; Simmerling, C., ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of chemical theory and computation 2015, 11 (8), 3696-3713.
18. Humphrey, W.; Dalke, A.; Schulten, K., VMD: visual molecular dynamics. Journal of molecular graphics 1996, 14 (1), 33-38.
19. Kumar, R.; Grubmuller, H., do_x3dna: a tool to analyze structural fluctuations of dsDNA or dsRNA from molecular dynamics simulations. Bioinformatics 2015, 31 (15), 2583-2585.
20. Abdel-Azeim, S.; Chermak, E.; Vangone, A.; Oliva, R.; Cavallo, L., MDcons: Intermolecular contact maps as a tool to analyze the interface of protein complexes from molecular dynamics trajectories. BMC Bioinformatics 2014, 15 (5), S1.
21. McAfee, J. G.; Edmondson, S. P.; Zegar, I.; Shriver, J. W., Equilibrium DNA Binding of Sac7d Protein from the Hyperthermophile Sulfolobus acidocaldarius:  Fluorescence and Circular Dichroism Studies. Biochemistry 1996, 35 (13), 4034-4045.
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