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論文中文名稱:以分子動態模擬探討野生型和△N6 β2-微球蛋白及其K3片段寡聚體的結構穩定性與其形成類澱粉沉積的關係 [以論文名稱查詢館藏系統]
論文英文名稱:Molecular Dynamics Simulations to Investigate the Relationships between the Structural Stability and Amyloidosis of the Wild-type and N-terminal Hexapeptide Deletion △N6 β2-Microglobulin and Its K3 Peptide Oligomers [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:生物科技研究所
出版年度:97
中文姓名:方柏盛
英文姓名:Po-Sheng Fang
研究生學號:95688014
學位類別:碩士
語文別:英文
口試日期:2008-07-18
論文頁數:118
指導教授中文名:劉宣良
指導教授英文名:Hsuan-Liang Liu
口試委員中文名:方旭偉;蔡偉博
口試委員英文名:Hsu-Wei Fang;Wei-Bor Tsai
中文關鍵詞:β2-微球蛋白透析相關性澱粉樣變△N6 β2-微球蛋白分子動態模擬鹽橋作用力K3區域類澱粉纖維2, 2, 2-三氟乙醇sheet-sheet 界面
英文關鍵詞:β2-microglobulin (β2m), dialysis-related amyloidosis (DRA)△N6 β2mamyloid formationmolecular dynamics (MD) simulationssalt-bridge interactionK3 peptidemorphologies2,2,2-trifluoroethanol (TFE)sheet-sheet interface
論文中文摘要:β2-微球蛋白(β2m)形成類澱粉纖維發生在需要長期血液透析的病人,進而導致透析相關性類澱粉病變(簡稱DRA)。從身體取出β2-微球蛋白所形的纖維發現蛋白質水解β2-微球蛋白的N端前六個胺基酸所產生的△N6 β2-微球蛋白的含量約有30%。過去實驗指出在中性pH值環境下,△N6 β2-微球蛋白比野生型(wt)β2-微球蛋白擁有更高的蛋白質聚集能力。為了獲得野生型和△N6 β2-微球蛋白在形成纖維之初始階段的原子尺度資訊,在本文中,利用不同組別的分子動態模擬,於不同溫度及中性pH值的環境中研究野生型和△N6 β2-微球蛋白的結構穩定性和動態過程。我們的模擬結果與先前的實驗結果一致,都證實△N6 β2-微球蛋白的結構穩定性比野生型β2-微球蛋白的結構穩定性來得低,這可歸因於△N6 β2-微球蛋白少了N端六個胺基酸而造成失去胺基酸R3與D59之間的鹽橋作用力,進而暴露K3(序列Ser20-Lys41)區域的結構。△N6 β2-微球蛋白暴露的K3區域使得水分子逐漸瓦解K3區域內部的結構,導致拉開strands B與E之間的距離,這個現象可能會加速△N6 β2-微球蛋白的結構變化,使得△N6 β2-微球蛋白能在中性pH值形成類澱粉纖維。因為△N6 β2-微球蛋白暴露K3區域,我們的結果推測K3區域可能是△N6 β2-微球蛋白聚集成纖維的成核點。由於他們擁有類似形成纖維中間體的結構,我們的結果也指出△N6 β2-微球蛋白在中性pH值所形成的纖維類似於野生型β2-微球蛋白在pH值1.5-3所形成的纖維。
上述實驗的結果顯示K3區域可能是△N6 β2-微球蛋白聚集成纖維的成核點,而已知K3胜肽可在不同pH值的水溶液及不同溶劑環境下形成纖維。最近的固態核磁共振結果研究成功地取得K3胜肽的原子結構座標,證實K3胜肽為一個U字型的β-strand-trun-β-strand結構。為了獲得K3胜肽在形成纖維之初始階段的原子尺度資訊,本研究以多組的分子動態模擬,於310 K和pH值2,分別在2, 2, 2-三氟乙醇(2,2,2-trifluoroethane,簡稱TFE)及水溶液的環境來研究不同大小規模的K3寡聚結構。在單層的寡聚實驗中,我們的結果顯示由於2, 2, 2-三氟乙醇破壞K3寡聚的疏水作用力,所以2, 2, 2-三氟乙醇會瓦解K3寡聚結構。我們更指出胺基酸Y7, F11, 和 I16所形成的疏水核心可穩定loop結構。我們的結果更推測K3胜肽形成類澱粉纖維的最低成核數是四聚。在雙層的寡聚實驗中,我們的結果證實K3胜肽可聚成不同sheet間的穩定結構,像是透過各自不同的作用力可形成NN、NC、CC界面的堆疊方式。我們進一步指出不同sheet與sheet之間的堆疊方式可能與在實驗中觀察到的K3胜肽會形不同形態的纖維有關,這樣的結果也與先前實驗的結果相呼應,先前實驗證實了將在2, 2, 2-三氟乙醇所形成的K3 protofibrils放到水溶液中,可形成4-15 nm直徑更粗的纖維。
論文英文摘要:β2-Microglobulin (β2m) forms amyloid fibrils in patients undergoing long-term hemodialysis, leading to dialysis-related amyloidosis (DRA). Proteolysis of the N-terminal region of β2m results in a truncation of the six N-terminal residues (△N6 β2m) in ~30% of the β2m molecules extracted from ex vivo fibrils. The △N6 β2m has been shown to exhibit a higher tendency for self-association comparing to the wild-type (wt) β2m, particularly at neutral pH. In order to gain atomic insights into the early stages of amyloid formation of the wt and △N6 β2m, various molecular dynamics (MD) simulations were conducted to investigate the stability and dynamics of these two molecules at various temperatures and neutral pH in this study. Our results, in agreement with previous experimental results, indicate that the structural stability of the △N6 β2m is lower than that of the wt β2m. It can be attributed to that the removal of the N-terminal six residues results in the loss of the salt-bridge interaction between residues R3 and D59, leading to the increased solvent exposure of the K3 peptide (Ser20-Lys41). It further allows water molecules to destabilize the interior region of the K3 peptide, leading to the elongation between the B- and E-strands. It may further accelerate the conformational changes of the △N6 β2m, leading to the formation of amyloid fibrils more readily at neutral pH. Our results also suggest that the K3 peptide may be a potential initiation site of amyloid formation for the △N6 β2m due to its increased solvent exposure. We further suggest that fibril morphology of the △N6 β2m formed at neutral pH is similar to that of the wt β2m formed at low pH (1.5-3) since they adopt the similar conformation with the elongation between B- and E-strands for their partially unfolded amyloidogenic intermediates.
The above computational results show that the K3 peptide, which has been known to form fibrils over a wide range of pH and solvent conditions, may be a potential initiation site of amyloid formation for the △N6 β2m. Recent solid-state NMR has revealed that K3 oligomer adopts a parallel U-shaped β-strand-turn-β-strand motif. In order to investigate the stability and morphologies of K3 oligomers with different sizes (dimer, trimer, and tetramer) and organizations (single and double layers), several all-atom molecular dynamics simulations were conducted at 310 K and pH 2 in water and 2,2,2-trifluoroethanol (TFE). For single-layered organizations, our results show that TFE destabilizes the stacking of K3 peptides due to the fact that TFE weakens the intermolecular hydrophobic interactions of K3 oligomers. In addition, we also identified that the loop region is stabilized by the hydrophobic cluster involving resides Y7, F11, and I16. Our results further suggest that K3 tetramer is a potential minimal nucleus seed for the formation of K3 protofibrils. For double-layered organizations in water, our data demonstrate that K3 peptides can form various stable assemblies through different interfacial arrangements, such as NN, NC, and CC, by different driving forces. We further propose that the stacking of different interfaces between two facing β-sheets of K3 peptides could be related to different fibril morphologies, which is in good agreement with the previous experimental results, showing that K3 protofibrils associated to formed mature fibrils with a wide range of diameters from 4 to 15 nm when they were transferred from 20% (v/v) TFE to aqueous solution.
論文目次:CONTENS
中文摘要 i
ABSTRACT iii
ACKNOWLEDGEMENTS vi
CONTENTS vii
TABLE CONTENTS xi
FIGURE CONTENTS xii
Chapter 1 GENERAL INTRODUCTION 1
Chapter 2 LITERATURE REVIEW 3
2.1 Amyloid 3
2.1.1 Dialysis-Related Amyloidosis 4
2.2.2 β2M Biological Function and Amyloidosis 4
2.2.3 Structure of β2M 5
2.2 Experimental and Theoretical Studies on β2M 8
2.2.1 Effect of pH on Fibril Morphology 8
2.2.2 Effect of Strands A and G on β2M 9
2.2.3 Different Intermediates Lead to Different Morphologies at Low pH 11
2.3 History of △N6 β2M 12
2.3.1 High Aggregation Ability at Physiological pH 13
2.4 Discovery of K3 Peptide 15
2.4.1 Structure of K3 Peptide 16
2.4.2 Effect of TFE and Aqueous Solutions on K3 Morphology 18
Chapter 3 MOLECULAR MODELING 19
3.1 Overview 19
3.2 Force Fields 20
3.2.1 Overview Several Main Types of Force Fields 20
3.2.2 The Parameters in the Force Fields 22
3.2.3 Functional Form of CVFF Force Field 28
3.3 Minimization 30
3.3.1 Minimization Algorithms 31
3.4 Equilibration 33
3.5 Molecular Dynamics 35
3.5.1 Dynamics 35
3.5.2 Constraints During Dynamics Simulations 37
3.5.3 Temperature Jump Techniques 39
3.6 Analysis 41
3.6.1 Root Mean Square Deviation 41
3.6.2 Contact Definition 42
3.6.3 Secondary Structure Prediction 42
3.6.4 Solvent Accessible Surface Area 43
3.6.5 Z-DOCK Program 44
3.6.6 Definition of Interstrand and Intersheet Distance 45
Chapter 4 Molecular Dynamics Simulations to Investigate the Structural Stability of Wild-type and N-terminal Hexapeptide Deletion △N6 β2-microglobulin ...47
4.1 Abstract 47
4.2 Introduction 48
4.3 Methods 52
4.3.1 The construction of the wt and △N6 β2m model 52
4.3.2 Structural Analyses and definition 53
4.4 Results 54
4.4.1 Analysis of Root Mean Square Deviation 54
4.4.2 Analysis of Secondary Structure contents 56
4.4.3 Analysis of the Distances between Residues R3 and D59 57
4.4.4 Analysis of the Solvent Accessible Surface Area of the K3 Peptide 59
4.4.5 Analysis of the SASA against the Cα distances between the B- and E-strands 61
4.5 Discussion 62
4.5.1 The △N6 β2m exhibit lower structural stability comparing to the wt β2m 62
4.5.2 The increased exposure of K3 peptide results in the elongation between B- and E-strands 63
4.5.3 The importance of the N-terminal six residues and salt-bridge interaction between R3-D59 64
4.5.4 Insights into the morphologies of amyloid fibrils of the △N6 β2m from MD simulations 66
4.6 Conclusions 67
4.7 References 68
Chapter 5 Molecular Dynamics Simulations to Gain Insights into the Stability and Morphologies of K3 Oligomers from β2-Microglobulin 73
5.1 Abstract 73
5.2 Introduction 74
5.3 Methodology 77
5.3.1 Construction of single- and double-layered K3 oligomers 77
5.3.2 Simulation protocol 79
5.3.3 Structural analyses 80
5.4 Results 81
5.4.1 Structural stability of single-layered K3 oligomers in water and TFE 81
5.4.2 The averaged interstrand distance and the β-sheet fraction per residue of single-layered K3 oligomers 82
5.4.3 The relationship between the hydrophobic contacts and the averaged interstrand distances of single-layered K3 oligomers 83
5.4.4 The effects of the hydrophobic residues in the loop region on the stability of single-layered K3 oligomers 85
5.4.5 Structural characteristics of double-layered K3 oligomers in water 87
5.4.6 The driving forces in maintaining the structural stability of double-layered K3 oligomers 90
5.5 Discussion 92
5.5.1 The effect of TFE and the role of the hydrophobic interactions on the stability of single-layered K3 oligomers 92
5.5.2 Minimal nucleus seed for single-layered K3 peptide in TFE 94
5.5.3 Loop stability plays a critical role in the formation of K3 protofibrils 95
5.5.4 Different interfacial arrangements form different fibril morphologies 95
5.6 Conclusions 96
5.7 References 98
Chapter 6 GENERAL CONCLUSIONS 105
6.1 General Conclusions 105
6.2 General Recommendations 106
Chapter 7 GENERAL REFERENCES 108
Appendex A 117

TABLE CONTENTS
Table 4.1 Averaged b-sheet contents of the wt and DN6 b2m at different temperatures
during the entire simulation courses. 57
Table 5.1 Summary of the labels and MD simulation conditions in the present study at 310 K and pH 2. 79
Table 5.2 The averaged SASAs (Å2) of the hydrophobic residues Y7, F11, and I16 located in the loop region for single-layered K3 oligomers at various solvent conditions during the 10-ns MD simulations. 87

FIGURE CONTENTS
Figure 2.1 X-ray crystallographic structure of wild-type b2m visualized by the Insight II program. 6
Figure 2.2 The connection diagram of seven β-strands from N to C terminus. 7
Figure 2.3 There are two β-sheets connected by the disulfide bond between Cys25 and Cys80. 7
Figure 2.4 Characterisation of different types of β2m amyloid-like fibrils formed in vitro at pH 3.5 (lefthand panels) and at pH 2.5 (righthand panels). 10
Figure 2.5 Negative stain EM images of samples of wild-type β2m and the variants △N6 at pH 7.0 in the absence of seed (A-B) or in the presence of heparin-stabilized seeds (D-E). 14
Figure 2.6 Schematic diagram showing the amyloid fibril formation from wild-type β2m at neutral pH. How the seeds are initially formed in vivo remains unknown. 15
Figure 2.7 3D structures of tetrameric K3 and monomeric K3 in the fibrillar state. 17
Figure 3.1 The illustrations for modeling of the bond, bond angle, torsion angle and charge-charge interactions in a model system. 27
Figure 3.2 The analytic form of the energy expression used in CVFF. 28
Figure 3.3 Morse vs. harmonic potentials. 29
Figure 3.4 Illustration of the energy relationship from the starting structure to MD simulation. 31
Figure 3.5 The method of Steepest Descent approaches the minimum in a zig-zag manner of energy surface. 32
Figure 3.6 Periodic boundary conditions (PBC) refers to the simulation of models consisting of a periodic lattice of identical subunits. 34
Figure 3.7 The distribution of velocity of water at various temperatures 40
Figure 3.8 The accessible surface of a molecule, defined as the locus of the center of a solvent molecule as it rolls over the van der Waals surface of the protein. 44
Figure 3.9 Definition of geometrical parameters for characterizing the structural organization of peptide oligomers 46
Figure 4.1 X-ray crystallographic structure of the wt b2m visualized by the Insight II program 50
Figure 4.2 (A) The Ca RMSD and (B) the Ca RMSD per residue of the wt and DN6 b2m at various temperatures during the 10-ns MD simulations 55
Figure 4.3 The secondary structures contents of the wt and DN6 b2m at 310K. 56
Figure 4.4 The distances of the salt-bridge interaction between the R3-D59 pair in the wt b2m at various temperatures during the 10-ns MD simulations 58
Figure 4.5 The solvent accessible surface area (SASA) of the K3 peptide of the wt and DN6 b2m in water at various temperatures during the 10-ns MD simulations 59
Figure 4.6 Solvation of the K3 peptide of the wt and DN6 b2m at 498K 60
Figure 4.7 The relationships between the SASA of the K3 peptide and the distance between the B- and E-strands of the wt and DN6 b2m at various temperatures during the 10-ns MD simulations 61
Figure 4.8 Snapshots of the averaged structures (per 2.5 ns) of the wt and DN6 b2m at 498K 62
Figure 4.9 Schematic representations of the amyloid morphologies and their related unfolding intermediates of the wt and △N6 β2m 67
Figure 5.1 Monomeric K3 peptide with each residue and top view of double-layered K3 oligomers with NN, NC, and CC interfacial arrangements 78
Figure 5.2 The averaged interstrand distances (dstrand) of single-layered K3 oligomers in water and TFE during the 10-ns MD simulations 82
Figure 5.3 The averaged interstrand distances (dstrand) and the b-sheet fraction per residue of single-layered K3 oligomers in water and TFE during the 10-ns MD simulations 84
Figure 5.4 The relationships between the fraction of the native hydrophobic contact and the averaged interstrand distance (dstrand) for single-layered K3 oligomers during the 10-ns MD simulations 86
Figure 5.5 Structural characteristics of double-layered K3 oligomers in water 89
Figure 5.6 The evolution of the number of the native hydrophobic contacts and the number of hydrogen bonds for double-layered K3 oligomers in water during the 5-ns MD simulations. 91
Figure 5.7 The averaged structures per 2.5 ns of double-layered K3 oligomers in water during the 5-ns MD simulations 93
論文參考文獻:Armen, R. S.; Daggett, V. Characterization of two distinct β2-microglobulin unfolding intermediates that may lead to amyloid fibrils of different morphology. Biochemistry 2005, 44, 16098-16107.
Bellotti, V.; Stoppini, M.; Mangione, P.; Sunde, M.; Robinson, C.; Asti, L.; Brancaccio, D.; Ferri, G. β2-Microglobulin can be refolded into a native state from ex vivo amyloid fibrils. Eur. J. Biochem. 1998, 258, 61-67.
Bellotti, V.; Gallieni, M.; Giorgetti, S.; Brancaccio, D. Dynamic of β2-microglobulin fibril formation and reabsorption: the role of proteolysis. Semin. Dial. 2001, 14, 117-122.
Borysik, A. J.; Radford, S. E.; Ashcroft, A. E. Co-populated conformational ensembles of β2-microglobulin uncovered quantitatively by electrospray ionization mass spectrometry. J. Biol. Chem. 2004, 279, 27069-27077.
Chelli, R.; Gervasio, F. L.; Procacci, P.; Schettino, V. Stacking and T-shape competition in aromatic-aromatic amino acid interactions. J. Am. Chem. Soc. 2002, 124, 6133-6143.
Chen, R.; Weng, Z. A. novel shape complementarity scoring function for protein-protein docking. Proteins 2003, 51, 397-408.
Chen, Y.; Dokholyan, N. V. A single disulfide bond differentiates aggregation pathways of β2-microglobulin. J. Mol. Biol. 2005, 354, 473-482.
Chiti, F.; Bucciantini, M.; Capanni, C.; Taddei, N.; Dobson, C. M.; Stefani, M. Solution conditions can promote formation of either amyloid protofilaments or mature fibrils from HypF N-terminal domain. Protein Sci. 2001, 10, 2541-2547.
Chiti, F.; Mangione, P.; Andreola, A.; Giorgetti, S.; Stefani, M.; Dobson, C. M.; Bellotti, V.; Taddei, N. Detection of two partially structured species in the folding process of the amyloidogenic protein β2-microglobulin. J. Mol. Biol. 2001, 307, 379-391.
Connors, L. H.; Shirahama, T.; Skinner, M.; Fenves, A.; Cohen, A. S. In vitro formation of amyloid fibrils from intact β2-microglobulin. Biochem. Biophys. Res. Commun. 1995, 131, 1063-1068.
Esposito, G.; Michelutti, R.; Verdone, G.; Viglino, P.; Hernandez, H.; Robinson, C. V.; Amoresano, A.; Dal Piaz, F., Monti, M.; Pucci, P.; Mangione, P.; Stoppini, M.; Merlini, G.; Ferri, G,; Bellotti, V. Removal of the N-terminal hexapeptide from human β2-microglobulin facilitates protein aggregation and fibril formation. Protein Sci. 2000, 9, 831-845.
Fändrich, M.; Dobson, C. M. The behaviour of polyamino acids reveals an inverse side chain effect in amyloid structure formation. EMBO J. 2002, 21, 5682-5690.
Ferguson, N.; Becker, J.; Tidow, H.; Tremmel, S.; Sharpe, T. D.; Krause, G.; Flinders, J.; Petrovich, M.; Berriman, J.; Oschkinat, H.; Fersht, A. R. General structural motifs of amyloid protofilaments. Proc. Natl. Acad. Sci. USA 2006, 103, 16248-16253.
Floege, J.; Ehlerding, G. β2-Microglogulin-associated amyloidosis. Nephron 1996, 72, 9-26.
Floege, J.; Ketteler, M. β2-Microglobulin derived amyloidosis: an update. Kidney Int. 2001, 59, 164-171.
Gejyo, F.; Yamada, T.; Odani, S.; Nakagawa, Y.; Arakawa, M.; Kunitomo, T.; Kataoka, H.; Suzuki, M.; Hirasawa, Y.; Shirahama, T.; Cohen, A. S.; Schmid, K. A new form of amyloid protein associated with chronic hemodialysis was identified as β2-microglobulin. Biochem. Biophys. Res. Commun. 1985, 129, 701-706.
Glenner, G. G. Amyloid deposits and amyloidosis. The beta-fibrilloses. N. Engl. J. Med. 1980, 302, 1283-1292.
Googman, J. M. Chemical Applications of Molecular Modeling. Cambridge: Royal Society of Chemistry 1998.
Gorevic, P. D.; Munoz, P. C.; Casey, T. T.; DiRaimondo, C. R.; Stone, W. J.; Prelli, F. C.; Rodrigues, M. M.; Poulik, M. D., Frangione, B. Polymerization of intact β2-microglobulin in tissue causes amyloidosis in patients on chronic hemodialysis. Proc. Natl. Acad. Sci. USA 1986, 83, 7908-7912.
Gosal, W. S.; Morten, I. J.; Hewitt, E. W.; Smith, D. A.; Thomson, N. H.; Radford, S. E. Competing pathways determine fibril morphology in the self-assembly of β-microglobulin into amyloid. J. Mol. Biol. 2005, 351, 850-864.
Heegaard, N. H.; Jorgensen, T. J.; Rozlosnik, N.; Corlin, D. B.; Pedersen, J. S.; Tempesta, A. G.; Roepstorff, P.; Bauer, R.; Nissen, M. H. Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved β2-microglobulin, Biochemistry 2005, 44, 4397-4407.
Hirota, N.; Mizuno, K.; Goto, Y. Group additive contributions to the alcohol-induced α-helix formation of melittin: implication for the mechanism of the alcohol effects on proteins. J. Mol. Biol. 1998, 275, 365-378.
Hoshino, M.; Katou, H.; Hagihama, Y.; Hasegawa, K.; Naiki, H.; Goto, Y. Mapping of the β2-microglobulin core by H/D exchange monitored by NMR. Nature Struct. Biol. 2002, 9, 323-325.
Inoue, S.; Kuroiwa, M.; Ohashi, K.; Hara, M.; Kisilevsky, R. Ultrastructural organization of hemodialysis-associated β2-microglobulin amyloid fibrils. Kidney Int. 1997, 52, 1543-1549.
Iwata, K.; Fujiwara, T.; Matsuki, Y.; Akutsu, H.; Takahashi, S.; Naiki, H.; Goto, Y. 3D structure of amyloid protofilaments of β2-microglobulin fragment probed by solid-state NMR. Proc. Natl. Acad. Sci. USA 2006, 103, 18119-18124.
Jimenez, J. L.; Guijarro, J. L.; Orlova, E.; Zurdo, J.; Dobson, C. M.; Sunde, M.; Saibil, H. R. Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. EMBO J. 1999, 18, 815-821.
Jones, S.; Smith, D. P.; Radford, S. E. Role of the N and C-terminal strands of β2-microglobulin in amyloid formation at neutral pH. J. Mol. Biol. 2003, 330 935-941.
Kad, N. M.; Thomson, N. H.; Smith, D. P.; Smith, D. A.; Radford, S. E. β2-Microglobulin and its deamidated variant, N17D form amyloid fibrils with a range of morphologies in vitro, J. Mol. Biol. 2001, 313, 559-571.
Kanno, T.; Yamaguchi, K.; Naiki, H.; Goto, Y.; Kawai, T. Association of thin filaments into thick filaments revealing the structural hierarchy of amyloid fibrils. J. Struct. Biol. 2005, 149, 213-218.
Kabsch, W.; Sander, C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 1983, 22, 2577-2637.
Klimov, D. K.; Thirumalai, D. Dissecting the assembly of Aβ16-22 amyloid peptides into antiparallel β sheets. Structure 2003, 11, 295-307.
Klunk, W. E.; Jacob, R. F.; Mason, R. P. Quantifying amyloid β-peptide (Aβ) aggregation using the Congo red-Aβ (CR-Aβ) spectrophotometric assay. Anal. Biochem. 1999, 266, 66-76.
Kozhukh, G. V.; Hagihara, Y.; Kawakami, T.; Hasegawa, K.; Naiki, H.; Goto, Y. Investigation of a peptide responsible for amyloid fibril formation of β2-microglobulin by achromobacter protease I. J. Biol. Chem. 2002, 277, 1310-1315.
Li, H.-T.; Du, H.-N.; Tang, L.; Hu, J.; Hu, H.-Y. Structural transformation and aggregation of human α-synuclein in trifluoroethanol. Biopolymers 2002, 64, 221-226.
Lucchi, L.; Fiore, G. B.; Guadagni, G.; Perrone, S.; Malaguti, V.; Caruso, F.; Fumero, R.; Albertazzi, A. Clinical evaluation of internal hemodiafiltration (iHDF): A diffusiveconvective technique performed with internal filtration enhanced high-flux dialyzers, Int. J. Artif. Organs 2004, 27, 414-419.
Lührs, T.; Ritter, C.; Adrian, M.; Riek-Loher, D.; Bohrmann, B.; Döbeli, H.; Schubert, D.; Riek, R. 3D structure of Alzheimer's amyloid-β(1-42) fibrils. Proc. Natl. Acad. Sci. USA 2005, 102, 17342-17347.
Ma, B.; Nussinov, R. Stabilities and conformations of Alzheimer’s β-amyloid peptide oligomers (Aβ16-22, Aβ16-35, and Aβ10-35): sequence effects. Proc. Natl. Acad. Sci. USA 2002, 99, 14126-14131.
Ma, B.; Nussinov, R. Molecular dynamics simulations of the unfolding of β2-microglobulin and its variants. Protein Eng. 2003, 11, 561-575.
Mandell, J. G.; Roberts, V. A.; Pique, M. E.; Kotlovyi, V.; Mitchell, J. C.; Nelson, E., Tsigelny, I., Ten Eyck, L. F. Protein docking using continuum electrostatics and geometric fit. Protein Eng. 2001, 14, 105-113.
McParland, V. J.; Kad, N. M.; Kalverda, A. P.; Brown, A.; Kirwin-Jones, P.; Hunter, M. G.; Sunde, M.; Radford, S. E. Partially unfolded states of β2-microglobulin and amyloid formation in vitro. Biochemistry 2000, 39, 8735-8746.
McParland, V. J.; Kalverda, A. P.; Homans, S. W.; Radford, S. E. Structural properties of an amyloid precursor of β2-microglobulin. Nat. Struct. Biol. 2002, 9, 326-331.
Miyazawa, S.; Jernigan, R. L. Estimation of effective inter-residue contact energies from protein crystal structures: quasi-chemical approximation. Macromolecules 1985, 18, 534-552.
Momany, F. A.; Rone, R. Validation of the general purpose QUANTA 3.2/CHARMm force field. J. Comp. Chem. 1992, 13, 888-900.
Monti, M.; Principe, S.; Giorgetti, S.; Mangione, P.; Merlini, G.; Clark, A.; Bellotti, V.; Amoresano, A.; Pucci, P. Topological investigation of amyloid fibrils obtained from β2-microglobulin. Protein Sci. 2002, 11, 2362-2369.
Morgan, C. J.; Gelfand, M.; Atreya, C.; Miranker, A. D. Kidney dialysis-associated amyloidosis: a molecular role for copper in fibre formation. J. Mol. Biol. 2001, 309, 339-345.
Mousseau, N.; Derreumaux, P. Exploring the early steps of amyloid peptide aggregation by computers. Acc. Chem. Res. 2005, 38, 885-891.
Myers, S. L.; Thomson, N. H.; Radford, S. E.; Ashcroft, A. E. Investigating the structural properties of amyloid-like fibrils formed in vitro from β2-microglobulin using limited proteolysis and electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 2006a, 20, 1628-1636.
Myers, S. L.; Jones, S.; Jahn, T. R.; Morten, I. J.; Tennent, G. A.; Hewitt, E. W.; Radford, S. E. A systematic study of the effect of physiological factors on β2-microglobulin amyloid formation at neutral pH. Biochemistry 2006b, 45, 2311-2321.
Naiki, H.; Higuchi, K.; Hosokawa, M.; Takeda, T. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, Thioflavin T1. Anal. Biochem. 1989, 177, 244-249.
Naiki, H.; Hashimoto, N.; Suzuki, S.; Kimura, H.; Nakakuki, K.; Gejyo, F. Establishment of a kinetic model of dialysis-related amyloid fibril extension in vitro. Amyloid Int. J. Expt. Clin. Invest. 1997, 4, 223-232.
Nguyen, H. D.; Hall. C. K. Spontaneous fibril formation by polyalanines: discontinuous molecular dynamics simulations. J. Am. Chem. Soc. 2006, 128, 1890-1901.
Nishi, S.; Ogino, S.; Maruyama, Y.; Honma, N.; Gejyo, F.; Morita, T.; Arakawa, M. Electron-microscopic and immunohistochemical study of β2-microglobulin-related amyloidosis. Nephron 1990, 56, 357-363.
Ohhashi, Y.; Hagihara, Y.; Kozhukh, G.; Hoshino, M.; Hasegawa, K.; Yamaguchi, I.; Naiki, H.; Goto, Y. The intrachain disulfide bond of β2-microglobulin is not essential for the Immunoglobulin fold at Neutral pH, but is essential for Amyloid Fibril formation at acidic pH. J. Biochem. 2002, 131, 45-52.
Prokuda, O. V.; Belosludov, V. R.; Igumenov, I. K.; Stabnikov, P. A. The calculation of Van der Waals interaction energy in the crystales of metal β-diketonates (metal= Al, Cr, Fe and Ir) J. Phys.: Conf. Ser. 2006, 29, 8-13.
Ritter, C.; Maddelein, M.-L.; Siemer, A. B.; Lührs, T.; Ernst, M.; Meier, B. H.; Saupe, S. J.; Riek, R. Correlation of structural elements and infectivity of the HET-s prion. Nature 2005, 435, 844-848.
Shrake, A.; Rupley, J. A. Environment and exposure to solvent of protein atoms. Lysozyme and insulin. J. Mol. Biol. 1973, 79: 351-371.
Smith, D. P.; Radford S. E. Role of the single disulphide bond of β2-microglobulin in amyloidosis in vitro. Protein Sci. 2001, 10, 1775-1784.
Smith, D. P.; Jones, S.; Serpell, L. C.; Sunde, M.; Radford, S. E. A systematic investigation into the effect of protein destabilisation on β2-microglobulin amyloid formation. J. Mol. Biol. 2003, 330, 943-954.
Sunde, M.; Blake, C. The structure of amyloid fibrils by electron microscopy and X-ray diffraction. Adv. Protein Chem. 1997, 50, 123-159.
Sunde, M.; Serpell, L. C.; Bartlam, M.; Fraser, P. E.; Pepys, M. B.; Blake, C. C. Common core structure of amyloid fibrils by synchrotron X-ray diffraction. J. Mol. Biol. 1997, 273, 729-739.
Trinh, C. H.; Smith, D. P.; Kalverda, A. P.; Phillips, S. E.; Radford, S. E. Crystal structure of monomeric human β2-microglobulin reveals clues to its amyloidogenic properties, Proc. Natl. Acad. Sci. USA 2002, 99, 9771-9776.
Tsai, H.-H.; Reches, M.; Tsai, C.-J.; Gunasekaran, K.; Gazit, E.; Nussinov, R. Energy landscape of amyloidogenic peptide oligomerization by parallel-tempering molecular dynamics simulation: significant role of Asn ladder. Proc. Natl. Acad. Sci. USA 2005, 102, 8174-8179.
Vakser, I. A. Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex. Proteins 1997, 1, 226-230.
Wadai, H.; Yamaguchi, K.; Takahashi, S.; Kanno, T.; Kawai, T.; Naiki, H.; Goto, Y. Stereospecific amyloid-like fibril formation by a peptide fragment of β2-microglobulin. Biochemistry 2005, 44, 157-164.
Westermark, P.; Benson, M. D.; Buxbaum, J. N.; Cohen, A. S.; Frangione, B.; Ikeda, S.; Masters, C. L.; Merlini, G.; Saraiva, M. J.; Sipe, J. D. Amyloid: toward terminology clarification. Report from the Nomenclature Committee of the International Society of Amyloidosis. Amyloid 2005, 12, 1-4.
Yamaguchi, I.; Hasegawa, K.; Takahashi, N.; Gejyo, F.; Naiki, H. Apolipoprotein E inhibits the depolymerization of β2-microglobulinrelated amyloid fibrils at a neutral pH. Biochemistry 2001, 40, 8499-8507.
Yamaguchi, K.; Takahashi, S.; Kawai, T.; Naiki, H.; Goto, Y. Seeding-dependent propagation and maturation of amyloid fibril conformation. J. Mol. Biol. 2005, 352, 952-960.
Yamamoto, S.; Yamaguchi, I.; Hasegawa, K.; Tsutsumi, S.; Goto, Y.; Gejyo, F.; Naiki, H. Glycosaminoglycans enhance the trifluoroethanolinduced extension of β2-microglobulin-related amyloid fibrils at a neutral pH. J. Am. Soc. Nephrol. 2004, 15, 126-133.
Yamamoto, S.; Hasegawa, K.; Yamaguchi, I.; Tsutsumi, S.; Kardos, J.; Goto, Y.; Gejyo, F.; Naiki, H. Low concentrations of sodium dodecyl sulfate induce the extension of β2-microglobulin-related amyloid fibrils at a neutral pH. Biochemistry 2005, 43, 11075-11082.
Zheng, J.; Ma, B.; Tsai, C.-J.; Nussinov, R. Structural stability and dynamics of an amyloid-forming peptide GNNQQNY from the yeast prion sup-35. Biophys. J. 2006, 91, 824-833.
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