類澱粉胜肽Abeta(25-35) 序列影響該類胜肽在水-膜環境下的組態: 強調多樣性的神經毒性

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石淵琪(Yuan-ci Shih) 查詢紙本館藏

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化學學系

論文名稱

類澱粉胜肽Abeta(25-35) 序列影響該類胜肽在水-膜環境下的組態: 強調多樣性的神經毒性
(Sequence Effects of Amyloid-Beta (25-35) Peptides on the Configurations within Membrane: Highlight for Diverse Neurotoxicities)

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摘要(中)

本篇論文利用replica-exchange molecular dynamics配合implicit membrane Born model 模擬阿茲海默症的致病蛋白， Abeta (25-35)，序列置換對其在水-膜環境下組態的變化。Abeta(25-35) 是全長Abeta的部分區段，但Abeta(25-35) 保留全長Abeta的特性與毒性。有趣的是Abeta(35-25) 卻不具有毒性。先前觀點認為Abeta胜肽的疏水性越高則毒性可能越強。因此本篇研究Abeta(25-35) 氨基酸序列對其在水-膜環境的組態差異。研究的四條胜肽分別為Abeta(25-35)、Abeta(25-35) 序列相反的Abeta(35-25)、親疏水胺基酸交錯的胜肽 (Abeta(25-35)-Alt) 與疏水性N端的胜肽(Abeta(25-35)-Shuffled)。模擬結果顯示膜環境可以誘導helix結構的生成。Helix結構的長度及穩定度會影響胜肽分布在膜疏水核心及膜親水區域的比例，且這四條胜肽的摺疊與穿膜有不同的行為。綜合胜肽在膜環境的二級結構與位置的關係，Abeta(35-25)具有較穩定的helix結構且擴散較Abeta(25-35) 慢，這些特性可能會使得Abeta(35-25)有較低程度的聚集，可以解釋為何Abeta(35-25)在實驗上不具有毒性。
第二部分利用全原子模型模擬Abeta(25-35)、N27A-Abeta(25-35) 與 M35A-Abeta(25-35) 三條胜肽在膜環境的結構與計算胜肽在膜上的擴散係數。模擬結果顯示胜肽在膜環境的二級結構與擴散係數和毒性的關係，此外，模擬結果發現Abeta(25-35)可膜上形成beta-bridge，beta-bridge可能作為一個模板加速Abeta在膜上amyloid fibril的形成。了解Abeta在膜環境的構型提供一個新的觀點，可以了解結構與神經毒性的關連與藥物設計達到降低Abeta聚集。

摘要(英)

The sequence effects of Alzheimer’s amyloid-beta fragment Abeta(25-35) on the configurations within membrane are investigated by replica-exchange molecular dynamics (MD) simulations with implicit membrane generalized Born model. Neurotoxicity of Abeta(25-35) is similar to the full length Abeta. Four peptides have same amino acids of Abeta(25-35), but with different sequences were simulated in a water-membrane environment. Although they have same amino acids, they have distinct configurations within membrane. Simulations show the membrane can induce the formation of helix structure. The helix length and stability of these four peptides are in the order of Abeta(25-35)-Shuffled > Abeta(35-25) > Abeta(25-35) > Abeta(25-35)-Alt. This order is in consistent with their fractions partitioned inside membrane’s hydrophobic core. These four peptides show different behaviors of interfacial folding and membrane insertion. The more structured and slower diffusion nature of Abeta(35-25) than those of Abeta(25-35) will lead to a lower degree of aggregation and consequently a lower neurotoxicity. This rationalization is in consistent with experimental results that Abeta(35-25) is nontoxic and vice versa. The second study employed all-atom long time-scale MD simulations to explore the configurations of Abeta(25-35), N27A-Abeta(25-35) and M35A-Abeta(25-35) aimed to rationalize their relative neurotoxicities. The relative neurotoxicities of these three peptides do not follow the general hydrophobicity-neurotoxicity relationships. We correlate their relative neurotoxicities with their relative mobilities and structures within membrane. This correlation is well rationalized by kinetics and thermodynamics. A stable beta-bridge structure of Abeta(25-35) is formed within membrane. We proposed this structure as a template in accelerating the amyloid formation within membrane. Understanding the configurations of Abeta peptides within membrane provides new insights to understand their neurotoxicities and give structure-based clues for rational drug design retarding amyloid aggregation.

關鍵字(中)

★ 胜肽
★ 組態

關鍵字(英)

★ Amyloid-Beta
★ Abeta
★ configuration

論文目次

中文摘要 i
Abstract ii
誌謝 iii
Table of Contents iv
List of Figures v
List of Tables vii
Introduction 1
Chapter Two 5
2-1 Methods 5
2-2 Results 10
2-2-1 Location of Peptide Residues within the Membrane 10
2-2-2 Secondary Structures of Peptides 12
2-2-3 Unpaired H-Bonding Sites of Peptides 15
2-2-4 Folding and Membrane Insertion Energy Landscape 15
2-3 Discussion 25
2-4 Conclusions and Summary 33
Chapter Three 35
3-1 Research Background and Motivations 35
3-2 Computational Methods 36
3-3 Results 38
3-3-1 Location of Peptide Residues within the Membrane 38
3-3-2 Secondary Structures of Peptides 42
3-3-3 Configurations of Peptides within Membrane 46
3-3-4 Unpaired H-Bonding Sites of Peptides 49
3-3-5 Stability of Aβ(25-35) β-bridge 49
3-3-6 Mobility of Peptide within Membrane 51
3-4 Discussion 52
3-5 Conclusions and Summary 55
References 56

參考文獻

1. Stefani, M., and C. M. Dobson. 2003. Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution. J. Mol. Med. 81:678-699.
2. Dobson, C. M. 2003. Protein folding and disease: a view from the first Horizon Symposium. Nat. Rev. Drug Discov. 2:154-160.
3. Rochet, J. C., and P. T. Lansbury. 2000. Amyloid fibrillogenesis: themes and variations. Current Opinion in Structural Biology 10:60-68.
4. Hardy, J., and D. J. Selkoe. 2002. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297:353-356.
5. Kayed, R., E. Head, J. L. Thompson, T. M. McIntire, S. C. Milton, C. W. Cotman, and C. G. Glabe. 2003. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300:486-489.
6. Walsh, D. M., I. Klyubin, J. V. Fadeeva, W. K. Cullen, R. Anwyl, M. S. Wolfe, M. J. Rowan, and D. J. Selkoe. 2002. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535-539.
7. Hartley, D. M., D. M. Walsh, C. P. P. Ye, T. Diehl, S. Vasquez, P. M. Vassilev, D. B. Teplow, and D. J. Selkoe. 1999. Protofibrillar intermediates of amyloid beta-protein induce acute electrophysiological changes and progressive neurotoxicity in cortical neurons. J. Neurosci. 19:8876-8884.
8. Lambert, M. P., A. K. Barlow, B. A. Chromy, C. Edwards, R. Freed, M. Liosatos, T. E. Morgan, I. Rozovsky, B. Trommer, K. L. Viola, P. Wals, C. Zhang, C. E. Finch, G. A. Krafft, and W. L. Klein. 1998. Diffusible, nonfibrillar ligands derived from A beta(1-42) are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U. S. A. 95:6448-6453.
9. Haass, C., and D. J. Selkoe. 2007. Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid [beta]-peptide. Nat Rev Mol Cell Biol 8:101-112.
10. Harper, J. D., S. S. Wong, C. M. Lieber, and P. T. Lansbury. 1999. Assembly of A beta amyloid protofibrils: An in vitro model for a possible early event in Alzheimer's disease. Biochemistry 38:8972-8980.
11. Lashuel, H. A., D. Hartley, B. M. Petre, T. Walz, and P. T. Lansbury. 2002. Neurodegenerative disease - Amyloid pores from pathogenic mutations. Nature 418:291-291.
12. Vassar, R., and M. Citron. 2000. A[beta]-Generating Enzymes: Recent Advances in [beta]- and [gamma]-Secretase Research. Neuron 27:419-422.
13. Crescenzi, O., S. Tomaselli, R. Guerrini, S. Salvadori, A. M. D'Ursi, P. A. Temussi, and D. Picone. 2002. Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment - Similarity with a virus fusion domain. Eur. J. Biochem. 269:5642-5648.
14. Sticht, H., P. Bayer, D. Willbold, S. Dames, C. Hilbich, K. Beyreuther, R. W. Frank, and P. Rösch. 1995. Structure of Amyloid A4-(1–40)-Peptide of Alzheimer's Disease. Eur. J. Biochem. 233:293-298.
15. Coles, M., W. Bicknell, A. A. Watson, D. P. Fairlie, and D. J. Craik. 1998. Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry 37:11064-11077.
16. Frozza, R. L., A. P. Horn, J. B. Hoppe, F. Simão, D. Gerhardt, R. A. Comiran, and C. G. Salbego. 2008. A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures. Neurochem. Res. 34:295-303.
17. Anfuso, C. D., G. Assero, G. Lupo, A. Nicotra, G. Cannavò, R. P. Strosznajder, P. Rapisarda, R. Pluta, and M. Alberghina. 2004. Amyloid [beta](1-42) and its [beta](25-35) fragment induce activation and membrane translocation of cytosolic phospholipase A2 in bovine retina capillary pericytes. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1686:125-138.
18. Pike, C. J., J. W.-W. Andrea, K. Joseph, H. C. David, G. G. Charles, and W. C. Carl. 1995. Structure-Activity Analyses of b-Amyloid Peptides: Contributions of the b25-35 Region to Aggregation and Neurotoxicity. J. Neurochem. 64:253-265.
19. Buche, R., E. Tavitian, D. RistigI, R. Swoboda, U. Stauss, H. U. Gremlich, L. De La Fourniere, M. Staufenbiel, P. Frey, and D. A. Lowe. 1996. Conformations of synthetic beta peptides in solid state and in aqueous solution Relation to toxicity in PC12 cells. Biochimica et biophysica acta. Molecular basis of disease 1315:40-46.
20. Kubo, T., S. Nishimura, Y. Kumagae, and I. Kaneko. 2002. In vivo conversion of racemized beta-amyloid ([D-Ser(26)]A beta 1-40) to truncated and toxic fragments ([D-Ser(26)]A beta 25-35/40) and fragment presence in the brains of Alzheimer's patients. J. Neurosci. Res. 70:474-483.
21. Misiti, F., B. Sampaolese, M. Pezzotti, S. Marini, M. Coletta, L. Ceccarelli, B. Giardina, and M. E. Clementi. 2005. A beta(31-35) peptide induce apoptosis in PC 12 cells: Contrast with A beta(25-35) peptide and examination of underlying mechanisms. Neurochemistry International 46:575-583.
22. Clementi, M. E., S. Marini, M. Coletta, F. Orsini, B. Giardina, and F. Misiti. 2005. A beta(31-35) and A beta(25-35) fragments of amyloid beta-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35. FEBS Lett. 579:2913-2918.
23. Lin, M. X., T. Mirzabekov, and B. L. Kagan. 1997. Channel formation by a neurotoxic prion protein fragment. J. Biol. Chem. 272:44-47.
24. Kagan, B. L., Y. Hirakura, R. Azimov, R. Azimova, and M. C. Lin. 2002. The channel hypothesis of Alzheimer's disease: current status. Peptides 23:1311-1315.
25. Lin, M. C. A., and B. L. Kagan. 2002. Electrophysiologic properties of channels induced by A beta 25- 35 in planar lipid bilayers. Peptides 23:1215-1228.
26. Wei, G. H., and J. E. Shea. 2006. Effects of solvent on the structure of the Alzheimer amyloid-beta(25-35) peptide. Biophys. J. 91:1638-1647.
27. Ma, B., and R. Nussinov. 2006. The Stability of Monomeric Intermediates Controls Amyloid Formation: Ab25-35 and its N27Q Mutant. Biophys. J. 90:3365-3374.
28. Tsai, H.-H. G., J.-B. Lee, S.-S. Tseng, X.-A. Pan, and Y.-C. Shih. 2010. Folding and membrane insertion of amyloid-beta (25-35) peptide and its mutants: Implications for aggregation and neurotoxicity. Proteins: Structure, Function, and Bioinformatics 78:1909-1925.
29. Sato, K., A. Wakamiya, T. Maeda, K. Noguchi, A. Takashima, and K. Imahori. 1995. Correlation among Secondary Structure, Amyloid Precursor Protein Accumulation, and Neurotoxicity of Amyloid b(25-35) Peptide as Analyzed by Single Alanine Substitution Journal of Biochemistry 118:1108-1111.
30. Dobson, C. M. 2003. Protein folding and misfolding. Nature 426:884-890.
31. Shearman, M. S., C. I. Ragan, and L. L. Iversen. 1994. Inhibition of PC12 cell redox activity is a specific, early indicator of the mechanism of beta-amyloid-mediated cell death. Proc. Natl. Acad. Sci. 91:1470-1474.
32. Hughes, E., R. M. Burke, and A. J. Doig. 2000. Inhibition of Toxicity in the β-Amyloid Peptide Fragment β-(25–35) Using N-Methylated Derivatives. J. Biol. Chem. 275:25109-25115.
33. Im, W., M. Feig, and C. L. Brooks. 2003. An implicit membrane generalized born theory for the study of structure, stability, and interactions of membrane proteins. Biophys. J. 85:2900-2918.
34. Im, W. P., M. S. Lee, and C. L. Brooks. 2003. Generalized born model with a simple smoothing function. J. Comput. Chem. 24:1691-1702.
35. Im, W., and C. L. Brooks. 2005. Interfacial folding and membrane insertion of designed peptides studied by molecular dynamics simulations. Proc. Natl. Acad. Sci. U. S. A. 102:6771-6776.
36. Lazaridis, T., and M. Karplus. 1999. Effective energy function for proteins in solution. Proteins-Structure Function and Genetics 35:133-152.
37. Still, W. C., A. Tempczyk, R. C. Hawley, and T. Hendrickson. 1990. Semianalytical treatment of solvation for molecular mechanics and dynamics. J. Am. Chem. Soc. 112:6127-6129.
38. Sugita, Y., and Y. Okamoto. 2000. Replica-exchange multicanonical algorithm and multicanonical replica-exchange method for simulating systems with rough energy landscape. Chem. Phys. Lett. 329:261-270.
39. Rao, F., and A. Caflisch. 2003. Replica exchange molecular dynamics simulations of reversible folding. J. Chem. Phys. 119:4035-4042.
40. Garcia, A. E., and J. N. Onuchic. 2003. Folding a protein in a computer: An atomic description of the folding/unfolding of protein A. Proc. Natl. Acad. Sci. U. S. A. 100:13898-13903.
41. Zhou, R. H. 2003. Trp-cage: Folding free energy landscape in explicit water. Proc. Natl. Acad. Sci. U. S. A. 100:13280-13285.
42. Pitera, J. W., and W. Swope. 2003. Understanding folding and design: Replica-exchange simulations of "Trp-cage" fly miniproteins. Proc. Natl. Acad. Sci. U. S. A. 100:7587-7592.
43. Felts, A. K., Y. Harano, E. Gallicchio, and R. M. Levy. 2004. Free energy surfaces of beta-hairpin and alpha-helical peptides generated by replica exchange molecular dynamics with the AGBNP implicit solvent model. Proteins-Structure Function and Bioinformatics 56:310-321.
44. Feig, M., J. Karanicolas, and I. C. L. Brooks. 2004. MMTSB Tool Set: enhanced sampling and multiscale modeling methods for applications in structural biology. J. Mol. Graphics Model. 22:377-395.
45. MacKerell, A. D., D. Bashford, M. Bellott, R. L. Dunbrack, J. D. Evanseck, M. J. Field, S. Fischer, J. Gao, H. Guo, S. Ha, D. Joseph-McCarthy, L. Kuchnir, K. Kuczera, F. T. K. Lau, C. Mattos, S. Michnick, T. Ngo, D. T. Nguyen, B. Prodhom, W. E. Reiher, B. Roux, M. Schlenkrich, J. C. Smith, R. Stote, J. Straub, M. Watanabe, J. Wiorkiewicz-Kuczera, D. Yin, and M. Karplus. 1998. All-atom empirical potential for molecular modeling and dynamics studies of proteins. J. Phys. Chem. B 102:3586-3616.
46. MacKerell, A. D., M. Feig, and C. L. Brooks. 2004. Improved treatment of the protein backbone in empirical force fields. J. Am. Chem. Soc. 126:698-699.
47. Ryckaert, J.-P., G. Ciccotti, and H. J. C. Berendsen. 1977. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J. Comp. Phys. 23:327-341.
48. Kumar, S., J. M. Rosenberg, D. Bouzida, R. H. Swendsen, and P. A. Kollman. 1995. Multidimensional Free-Energy Calculations Using the Weighted Histogram Analysis Method. J. Comput. Chem. 16:1339-1350.
49. Kabsch, W., and C. Sander. 1983. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577-2637.
50. Williamson, R., and C. Sutherland. 2011. Neuronal Membranes are Key to the Pathogenesis of Alzheimers Disease: the Role of Both Raft and Non-Raft Membrane Domains. Current Alzheimer Research 8:213-221.
51. D'Ursi, A. M., M. R. Armenante, R. Guerrini, S. Salvadori, G. Sorrentino, and D. Picone. 2004. Solution structure of amyloid beta-peptide (25-35) in different media. J. Med. Chem. 47:4231-4238.
52. Kohno, T., K. Kobayashi, T. Maeda, K. Sato, and A. Takashima. 1996. Three-dimensional structures of the amyloid beta peptide (25-35) in membrane-mimicking environment. Biochemistry 35:16094-16104.
53. Demuro, A., E. Mina, R. Kayed, S. C. Milton, I. Parker, and C. G. Glabe. 2005. Calcium Dysregulation and Membrane Disruption as a Ubiquitous Neurotoxic Mechanism of Soluble Amyloid Oligomers. J. Biol. Chem. 280:17294-17300.
54. Shanmugam, G., and P. L. Polavarapu. 2004. Structure of A beta(25-35) peptide in different environments. Biophys. J. 87:622-630.
55. Terzi, E., G. Holzemann, and J. Seelig. 1994. Reversible Random Coil Beta-Sheet Transition of the Alzheimer Beta-Amyloid Fragment (25-35). Biochemistry 33:1345-1350.
56. Millucci, L., L. Ghezzi, G. Bernardini, and A. Santucci. 2010. Conformations and Biological Activities of Amyloid Beta Peptide 25-35. Curr. Protein Peptide Sci. 11:54-67.
57. White, S. H., and W. C. Wimley. 1999. Membrane Protein Folding and Stability: Physical Principles. Annu. Rev. Biophys. Biomolec. Struct. 28:319-365.
58. Jaud, S., M. Fernandez-Vidal, I. Nilsson, N. M. Meindl-Beinker, N. C. Hubner, D. J. Tobias, G. von Heijne, and S. H. White. 2009. Insertion of short transmembrane helices by the Sec61 translocon. Proc. Natl. Acad. Sci. 106:11588-11593.
59. Ulmschneider, M. B., J. C. Smith, and J. P. Ulmschneider. 2010. Peptide Partitioning Properties from Direct Insertion Studies. Biophys. J. 98:L60-L62.
60. Miyashita, N., J. E. Straub, and D. Thirumalai. 2009. Structures of b-Amyloid Peptide 1-40, 1-42, and 1-55 - the 672-726 Fragment of APP in a Membrane Environment with Implications for Interactions with g-Secretase. J. Am. Chem. Soc. 131:17843-17852.
61. Terzi, E., G. Holzemann, and J. Seelig. 1994. Alzheimer Beta-Amyloid Peptide-25-35 - Electrostatic Interactions with Phospholipid-Membranes. Biochemistry 33:7434-7441.
62. Dante, S., T. Hauss, and N. A. Dencher. 2003. Insertion of externally administered amyloid beta peptide 25-35 and perturbation of lipid bilayers. Biochemistry 42:13667-13672.
63. Tsai, C.-W., N.-Y. Hsu, C.-H. Wang, C.-Y. Lu, Y. Chang, H.-H. G. Tsai, and R.-C. Ruaan. 2009. Coupling Molecular Dynamics Simulations with Experiments for the Rational Design of Indolicidin-Analogous Antimicrobial Peptides. Journal of Molecular Biology 392:837-854.
64. Chang, Z., Y. Luo, Y. Zhang, and G. Wei. 2011. Interactions of Aβ25−35 β-Barrel-like Oligomers with Anionic Lipid Bilayer and Resulting Membrane Leakage: An All-Atom Molecular Dynamics Study. J. Phys. Chem. B 115:1165-1174.
65. Ulmschneider, J. P., M. Andersson, and M. B. Ulmschneider. 2010. Determining Peptide Partitioning Properties via Computer Simulation. The Journal of Membrane Biology 239:15-26.
66. Jo, S., T. Kim, V. G. Iyer, and W. Im. 2008. CHARMM-GUI: A web-based graphical user interface for CHARMM. J. Comput. Chem. 29:1859-1865.
67. Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: Visual molecular dynamics. J. Mol. Graph. 14:33-38.
68. Klauda, J. B., R. M. Venable, J. A. Freites, J. W. O'Connor, D. J. Tobias, C. Mondragon-Ramirez, I. Vorobyov, A. D. MacKerell, and R. W. Pastor. 2010. Update of the CHARMM All-Atom Additive Force Field for Lipids: Validation on Six Lipid Types. J. Phys. Chem. B 114:7830-7843.
69. Jorgensen, W. L., J. Chandrasekhar, J. D. Madura, R. W. Impey, and M. L. Klein. 1983. Comparison of Simple Potential Functions for Simulating Liquid Water. J. Chem. Phys. 79:926-935.
70. Kale, L., R. Skeel, M. Bhandarkar, R. Brunner, A. Gursoy, N. Krawetz, J. Phillips, A. Shinozaki, K. Varadarajan, and K. Schulten. 1999. NAMD2: Greater scalability for parallel molecular dynamics. J. Comp. Phys. 151:283-312.
71. Hoover, W. G. 1985. Canonical dynamics: Equilibrium phase-space distributions. Phys. Rev. A. 31:1695.
72. Feller, S. E., Y. H. Zhang, R. W. Pastor, and B. R. Brooks. 1995. Constant-Pressure Molecular-Dynamics Simulation - the Langevin Piston Method. J. Chem. Phys. 103:4613-4621.
73. Steinbach, P. J., and B. R. Brooks. 1994. New Spherical-Cutoff Methods for Long-Range Forces in Macromolecular Simulation. J. Comput. Chem. 15:667-683.

指導教授

蔡惠旭(Hui-Hsu Gavin Tsai)

審核日期

2011-7-26

推文