(3.237.20.246) 您好!臺灣時間:2021/04/16 07:51
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:張家萌
研究生(外文):chia-mon Chang
論文名稱:a1-antitrypsinderivedC-terminalpeptide(C36)之結構研究
論文名稱(外文):Studies on solution structures of a1-antutrypsin derived C-terminal peptide (C36)
指導教授:鄭梅芬
指導教授(外文):mei-feng Jeng
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生物科技研究所碩博士班
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:2003
畢業學年度:91
語文別:中文
論文頁數:102
中文關鍵詞:抗胰蛋白結構
外文關鍵詞:a1-antitrypsinstructure C-terminal peptide
相關次數:
  • 被引用被引用:1
  • 點閱點閱:103
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
人類抗胰蛋白酵素利用它本身具有可與目標物作用的彎曲結構(loop) (Lomas and Carrell, 1993) 與目標物結合且經過一個不可逆的過程形成1:1 的複合物(Pemberton et al., 1988),在此複合物形成的同時,抗胰蛋白酵素C 端上會有一段36 個氨基酸的序列(C36) 被水解出來(Carrell et al., 1979),此段胜 會形成β-澱粉性蛋白纖維(β
amyloid fibril),造成澱粉狀蛋白沉澱引起病變。直至目前為止C36 形成纖維沉澱的機制尚不清楚,只知道與造成阿滋海默症的蛋白質沉澱機制相仿,並且抗胰蛋白酵素在不同的情形下會促進或是抑制澱粉性蛋白纖維化的形成。此段胜 具有許多的生理功能,如:它會經由氧化機制而促使人類單核球(monocyte) 的活化(Bironait et al., 2001)並刺激過氧小體增生活化受體(peroxisome proliferation-activated receptors ) α、γ的產生而導致細胞間脂肪的累積,進而在心血管壁形成粥狀硬化斑。
在此論文中,我們使用核磁共振(nuclear magnetic resonance)及CD 光譜的方法在不同之仿膜環境及酸鹼值下研究抗胰蛋白酵素C 端上C36 的結構變化,希望藉由觀測結構的變化能進一步推測此
段胜 形成β-澱粉性蛋白纖維的機制及其結構與功能的關係。
C36 在水溶液及仿膜環境(SDS micelle, DPC micelle and TFE) 中
在不同的酸鹼值之下,由CD 光譜的結果發現: (1) 在水溶液中,
II
á-helix 的量會隨著酸鹼值的提高而減少,而â-sheet 結構隨著酸鹼值
之提高而增加。(2) 在TFE 以及DPC 仿膜環境下,á-helix 的量會隨
著酸鹼值的提高而增加而â-sheet 結構隨著酸鹼值之提高而減少。(3)
在SDS micelle 中,C36 所具有â-strand 的量是較在TFE 中多的。(4)
SDS micelle 中,當酸鹼值小於7.4 時,C36 的二級結構幾乎相同。
而酸鹼值提高時,C36 的â-strand 量減少而á-helix 的量增加,一般
情況下,â-strand 會形成â-fibril 結構,而á-helix 則否,這暗示在仿
酸性膜環境下,類似生理pH 值下,當pH 值稍微減少就會造成â 纖
維之產生。(5) TFE 有助於C36 中á-helix 結構的穩定及促進。
再者我們利用核磁共振法計算C36 在SDS 微粒中的結構,由初
步結果看來推測C36 具有三個â- strand,猜測C36 的â- sheet 聚集形
成纖維結構進而集結為斑塊造成疾病。之前會形成澱粉性β纖維之胜
以核磁共振法得到的結構都是以á-helix 存在的,但是與實際病理
情況不同,無法在溶液中研究澱粉性β纖維胜 之結構。我們發現在
溶液中澱粉性β纖維胜 亦可以â-strand 纖維結構存在,使得在溶液
中研究澱粉性蛋白的機制變為可行。
á1-antitrypsin (AAT) is an inhibitor of serine protease in general and its most
important target enzyme is neutrophil elastase. AAT, like other serpins, presents a
reactive site region as a proteinase accessible loop, thus mimicking an ideal substrate
to the target enzyme. Formation of a 1:1 molar complex between serpin and enzyme
is accompanied by an irreversible molecular transition of AAT. Following complex
formation and hydrolysis of the reactive site peptide bond, a ~ 4 kDa carboxy terminal
fragment of the inhibitor is generated (C36). C36 has been pronounced tendency to
aggregate and form amyloid fibrils. C36 fibrils morphologically appear very similar
to Alzheimer amyloid â fibrils formation. This peptide is involved in many
physiological functions: It regulates inflammatory transcription factors in primary
human monocytes and activates the production of PPARá, PPARã which will result in
atherosclerosis. C36 peptide has been found in atherosclerosclerotic plaques,
therefore C36 might play an important role in the pathogenesis of atherosclerosis.
á1-antitrypsin may influence amyloid â fibril processing, affecting both promotion
and inhibition of fibrillogenesis. Detailed examination of C36 structure will lead
us to a better elucidation for the structure determinants regarding its mechanism for
amyloid fibril formation and its structure-function relationship.
First, circular dichroic spectra of C36 in aqueous solution-2mM SDS/10mM
Na2HPO4 and in different membrane-mimicking environment 240mM SDS micelle ,
3 mM DPC micelle and 60% TFE at various pH indicate that (i) the content of á-helix
structure of C36 in aqueous solution contain 2 mM SDS is increased with decrease of
pH. (ii) the content of á-helix structure of C36 in TFE membrane—mimicking
environment is higher with increase of pH. (iii) in SDS micelle, C36 contains more
â-strand structures than in TFE. (iv) in SDS micelle, the secondary structures of
C36 are almost the same when pH below 7.4. C36 forms more â-stranded structure
IV
at lower pH than at pH > 8. This phenomen is similar to that in physiological
condition. Under physiological condition, more â-stranded structure facilitates C36
to form a thinned-out fibrous cap of atherosclerosis plaque . (v) in TFE, C36
facilitates á-helix structure.
We prospected the solution structure of C36 in the sodium dodecyl sulphate
(SDS) micelle, pH 4.8, by NMR method it exists three â-strands. Unlike other
solution structure of amyloid peptide which forms á-helix in SDS micelle, we
proposed that threeβstrands protofilaments will then aggregate to form fibrils which
result in plaque. These results may suggest that C36 may provide a good model for
the investigation of Amyloid fibril formation.
目錄
中文摘要… … … … … … … … … … … … … … … … … … … …. . I
英文摘要… … … … … … … … … … … … … … … … … … … …... III
誌謝… … … … … … … … … … … … … … … … … … … ….. V
目錄… … … … … … … … … … … … … … … … … … … . . .... VI
圖目錄… … … … … … … … … … … … … … … … … … … . . .... IX
表目錄… … … … … … … … … … … … … … … … … … …...... XI
附錄… … … … … … … … … … … … … … … … … … …..... XII
縮寫檢索表… … … … … … … … … … … … … … … … … … … XIII
第一章研究主題背景… … … … … … … … … … … … … … … … … … … 1
1-1 澱粉狀蛋白沉澱的概述… … … … … … … … … … … … … … … … … . 1
1-2 抗胰蛋白酵素C 端胜 之特性及生理功能… … … … … … … … … 7
1-3 核磁共振決定蛋白質結構之介紹… … … … … … … … … … … .....13
1-4 CD 光譜儀測量蛋白質二級結構之介紹… … … … … … … … …....15
1-5 論文研究動機、策略及目的… … … … … … … … … … … … … … … 17
第二章研究材料及方法… … … … … … … … … … … … … … … … … … 21
2-1 樣品製備… … … … … … … … … … … … … … … … … … … … …...21
2-2 CD 光譜儀的測定… … … … … … … … … … … … … … … … … … ….21
2-3 NMR光譜的測定… … … … … … … … … … … … … … … … … … …..22
2-4 利用NMR 方法決定蛋白質的三度空間結構… … … … … … … ….22
(一) 蛋白質的1H NMR 光譜判定
a. 質子自旋系統判定(Spin-system assignment)… … … … … ….23
b. 循序判定(Sequential assignment)… … … … … … … … … … … 23
c.分子結構的限制條件… … … … … … … … … … … … … … … … ….24
(二) 結構計算… … … … … … … … … … … … … … … … … … … … … ….26
(三) 三度空間結構的顯示與排列(alignment)… … … … … … … … … 30
第三章實驗結果… … … … … … … … … … … … … … … … … … … … … 32
3-1 CD光譜儀測量抗胰蛋白酵素C 端胜 之二級結構… … … … … 32
3-2 C 36 之NMR 圖譜的分析… … … … … … … … … … … … … … …..38
a. C36 之二級結構分析… … … … … … … … … … … … … … …. … .38
b. C36 的三度空間立體結構… … … … … … … … … … … … … … ...... 39
第四章討論… … … … … … … … … … … … … … … … … … … … … … … 41
4-1 C 36 形成纖維化之機制與酸鹼值及仿膜環境的關係探討… … …43
4-2 C36 在溶液中的結構與過去澱粉性蛋白纖維研究的比較… … …44
第五章結論… … … … … … … … … … … … … … … … … … … … … … … 47
參考文獻… … … … … … … … … … … … … … … … … … … … … … …..49
圖… … … … … … … … … … … … … … … … … … … … … … … … …..58
表… … … … … … … … … … … … … … … … … … … … … … … … …..73
附圖… … … … … … … … … … … … … … … … … … … … … … … …..78
自述… … … … … … … … … … … … … … … … … … … … … … … …..87
圖目錄
圖1-1 抗胰蛋白酵素的氨基酸序列… … … … … … … … … … … … … 58
圖1-2 抗胰蛋白酵素的第383 到391 的氨基酸序列… … … … … … 59
圖2-1 結構計算流程圖… … … … … … … … … … … … … … … … … … 60
圖3-1 C36 溶於2 mM SDS/ NaH2PO4, pH 4.5-8 的CD 光譜… …..61
圖3-2 C36溶於240 mM SDS/ NaH2PO4, pH 4.5-8的CD光譜… … .61
圖3-3 C36 溶於240 mM SDS/ NaH2PO4, pH 值為7-8 的CD光譜..62
圖3-4 C36 溶於240 mM SDS/ NaH2PO4, pH 值為7.3-7.5 的CD光譜… … … … … … … 62
圖3-5 C36 溶於60 % TFE /10 mM NaH2PO4溶液中,pH值為4.5-8的CD光譜… … … … …… 圖3-6 C36 溶於3 mM DPC/ NaH2PO4 溶液中,pH 值為4.5~8 的CD 光譜… … … … … ..63
圖3-7 C36 溶於不同仿膜環境下,pH 4.5 及7 的CD 光譜比較.....64
圖3-8 C36 的DQF- COSY 圖譜… … … … … … … … … … … … …... … 65
圖3-9 C36 的2D-TOCSY圖譜… … … … … … … … … … … … … … … .66
圖3-10 C36 的2D-NOESY圖譜… … … … … … … … … … … … … … .67
圖3-11 C36 在NOESY 光譜作循序判定的結果… … … … … … … . .68
圖3-12 C36 之Cá 化學位移值與random coil 之化學位移值的差異… …… … … …..69
圖3-13 C36 的三度空間立體圖… … … … … … … … … … … … … … ...70
圖3-14 初步計算的C36 的Ramanchandran 圖… … … … … … … … . .71
表目錄
表3-1 C 36 的CD光譜二級結構含量表… … … … … … … … … … ….72
表3-2 C36 之化學位移表… … … … … … … … … … … … … … … … …73
表3-3 C 36 之序列(sequential, i+1) 和中距離(Medium,i+2~4)NOE 的連結情形…… 74
表3-4 C36 結構計算統計表… … … … … … … … … … … … … … … …75
附錄
附圖1-1 利用核磁共振法計算結構之基本理論圖… … … … … …...76
附圖1-2 線性二色性… … … … … … … … … … … … … … … … … …...77
附圖1-3 平面偏振光經由磁圓二色性轉換為橢圓偏振光… … …...78
附圖1-4 直線偏極光與圓形偏極光的電向量… … … … … … … …...79
附圖1-5 蛋白質二級結構之CD 光譜… … … … … … … … … … ….80
附圖2-1 各種氨基酸1H NMR 光譜化學位移分布圖… … … … …..81
附圖2-2 利用TOCSY/NOESY圖譜循序判定… … … … … … … …..82
附圖4-1 澱粉性蛋白形成纖維的過程… … … … … … … … … … …..83
附表2-1 20 種氨基酸殘基在random coil 結構下的氫質子化學位移…… … …84
附表2-2 蛋白質各種二級結構的原子間距… … … … … … … … …...85
Abraham, C. R., Selkoe, D. J., and Potter, H. Immunochemical
identification of the serine protease inhibitor á1-antichymotrypsin in the
brain amyloid deposits of Alzheimer’s disease. Cell 52, 487-501. 1998
Alder, A. J., Greenfield, N. J. and Fasman, D. G Circular Dichroism and
Optical Rotary Dispersion of Proteins and Polypeptides, Meth.
Antzutkin O. N., Balbach J. J., Tycko R. Site-Specific identification of
non-beta-strand conformations in Alzheimer''s beta-amyloid fibrils by
solid-state NMR. Biophys J. 84, 3326-3335. 2003
Asteas T. P., Ishii Y., Balbach J. J., Antzutkin O. N., Leapman R. D. and
Tycko, R.A structural model for Alzheimer’s â fibril based on
experimental constraints from solid state NMR. Proc. Nat. Acad. Sci.
Asien, P. S., and Davis, K. L. Inflammatory mechanisms in Alzheimer’s
disease: Implications for therapy. Am. J. Psychiatry 151, 1105-1113. 1994
Badmen, M. K., Pryce, R A., Charge, S. B., Morris, J. F., and Clark, A.
Fibrillar islet amyloid polypeptide (amylin) is internalised by
macrophages but resist proteolytic degradation. Cell Tissue Res. 291,
Barrow, C. J., and Zagorski, M. G., Solution structures of â peptide and
its constituent fragments: Relation to amyloid deposition. Science 253,
182. 1991
Benzinger T. L., Gregory D. M., Burkoth T. S., Miller-Auer H., Lynn D.
G., Botto R. E., Meredith S. C., Two-dimensional structure of
beta-amyloid (10-35) fibrils. Biochemistry 39, 3491-3499. 2000
Bousquet, J. A., Garbay, C., Roques, B. P. and Mely, Y. Circular dichroic
investigation of the native and non-native conformational states of the
growth factor receptor-binding oritein 2 N-terminal src homology domain
3: effect of binding to a praline-rich peptide from guanine nucleotide
exchange factor. Biochemistry 39, 7722-7735. 2000
Brodbeck, R. M., Brown, J. L. Secretion of á1-proteinase inhibitor
requires an almost full length molecule. J. Biol.Chem. 264, 294-297. 1992
Carrell, R. W., Owen, M., Brennan, S., and Vaughn, L. Carboxy terminal
cleavage: Homology with antithrombin III. Biochem. Biophys. Res.
Commun 91, 1032-1037. 1979
Carrell, R.W., and Evans, D. L. I. Serpins: Mobile conformations in a
family of proteinase inhibitors. Curr. Opinion Structural Biol. 2, 438-446.
1992
Carrell, R. W. and Lomas, D. A. Conformational disease. Lancet 350,
134-138. 1997
Cataldo, A. M. and Nixon, R. A. Enzymatically active lysosomal protease
are associated with amyloid deposits in Alzheimer brain. Proc Natl Acad
Sci.USA 87, 3861-3865. 1990
Coles, M., Bicknell W., Watson A. A., Fairlie D. P and Daugh C.
A.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, 11064-77. 1998
Chiti, F., Webster, P., Taddei, N., Clark, A., Steffani, M., Ramponi, G. and
Dobson, C. M. Designing condition for in vitro formation of amyloid
protofilaments and fibrils. Proc. Natl. Acad. Sci. USA 96, 3590-3594.
1999
Chou, P. Y., Fasman, G. D. Conformational parameters for amino acids
in helical, beta-sheet, and random coil regions calculated from proteins.
Biochemistry 13, 211-222. 1974
David, H., Mutter, P., Glover, G. I., Rivetna, M., Schasteen, C. S., and
Fallon R. J. Identification of a serpin-enzyme complex receptor on human
hepatoma cells anf human monocytes. Proc. Natl. Acad. Sci. USA 87.
3753-3757. 1990
Diringer, H. Hidden amyloidoses. Exp. Clin. Immunogenet 9, 212-229.
1992
Dobson, C. M. Protein misfolding, evolution and disease. Trends Biochem.
Sci. 24, 329-332. 1999
Fabrizio, N. P. W., Anne, T., Massino, C. Designing conditions for in vitro
formation of amyloid protofilaments and fibrils. Pro.c Natl. Acad. Sci.
USA 96, 3590-3594. 1999
Garnier J., Osguthorpe, D. J., Robson, B, Analysis of the accuracy and
implications of simple methods for predicting the secondary structure of
globular proteins. J. Mol. Biol. 120, 97-120. 1978
George, A. R., Howlett, D. R. Computationally derived structural models
of the â-amyloid found in Alzheimer''s disease plaques and the interaction
with possible aggregation inhibitors. Biopolymers 50, 733-741. 1999
Gregory, D. M., Benzinger, T. S., Burkoth, T. S., Miller A. H., Lynn, D.
G., Botto, R. E., and Meredith, S. C. Dipolar recoupling NMR of
biomolecular self-assemblies: determining inter- and intra-strand
distances in fibrilized Alzheimer''s â-amyloid peptide. Solid State Nucl.
Magn. Reson. 13, 149-166. 1998
Gustavsson, A., Engström, U., and Westemark, P. Mechanisms of
transthyretin amyloidogenesis. Antigenic mapping of transthyretin
purified from plasma and amyloid fibrils and within in situ tissue
localizations. Am. J. Pathol. 144, 1301-1311. 1994
Shao, H., Jao, S. C., and Zagorski, M. G. Solution Structure of
micelle-bound amyloid â-(1-40) and â-(1-42) peptide of Alzheimer’s
disease. J. Mol. Biol. 285, 755 - 773. 1999
Ishii, T., and Hega, S. Complements, microglial cells and amyloid fibril
formation. Res. Immunol. 143, 614-616. 1992
Janciauskiene, S., Carlemalm, E., Eriksson, S. In vitro fibril formation
from α 1-antitrypsin -derived C-terminal peptides. Biol Chem
Hoppe-Seyler 376, 415-423. 1995
Janciauskiene, S., Lindgren, S., Wright, H. T. The C-terminal peptide of
α1-antitrypsin increases low density lipoprotein binding in HepG2 cells.
Eur.J.Biochem. 254, 460-467. 1998
Janciauskiene, S., Dichtl, W., Moraga, F., Ares, M. P., Crisby M., Nilsson
J., Lindgren S. The carboxyl-terminal fragment of α1-antitrypsin is
present in atherosclerotic plaques and regulated inflammatory
transcription factors in primary human monocytes. Mol. Cell. Biol. Res.
Commun. 4, 50-61. 2000
Johnson, W. C. The fractions of secondary structures from the CDsstr
program (variable selection method) Proteins: Struc. Func. Genet. 35,
307-312. Program Modified by Sreerama, N. 1999
Johansson, J., Gröndal, S., Sjövall, J., Jörnall, H., and Curstedt, T.
Identification of hydrophobic fragments of á1-antitrypsin and C1 protease
inhibitor in human bile, plasma and spleen. FEBS Lett. 299, 146-148.
1992
Kalaria, R. N., and Grahovac, L. Serum amyloid P immunoreactivity in
hippocampal tangles, plaques and vessels: Implications for leakage across
the blood-brain barrier in Alzheimer’s disease. Brain. Res. 516, 349-353.
1990
Koga, T., Taguchi, K., Kobuke, Y., Kinoshita, T., and Higuchi, M.
Structure regulation of a peptide-conjugated graft copolymer: a simple
model for amyloid formation. Chem. 9 1146-1156. 2003
Klein, W. L., Krafft, G. A. and Finch, C. E. Targeting small Aâ oligomers:
the solution of an Alzheimer’s disease conundrum? Trends Neurosci. 24,
219-224. Review. 2001
Known, K.-S., Kim, J., Shin, H. S., and Yu, M.-H. Single amino acid
substitutions of á1-antitrypsin that confer enhancement in thermal stability.
J. Biol. Chem. 269, 9627-9631. 1994
Lansbury, P. T., Costa P. R., Griffiths, J. M., Simon, E. J., Auger, M.,
Halverson, K. J., Kocisko, D. A., Hendsch, Z. S., Ashburn, T. T., Spencer,
R. G. Structural model for the beta-amyloid fibril based on interstrand
alignment of an antiparallel-sheet comprising a C-terminal peptide. Nat.
Struct. Biol. 2, 990-998. 1995
Lazo, N. D. and Downing, D. T. Amyloid fibrils may be assembled from
â-helical protofibrils Biochemistry 37, 1731 -1735, 1998
Lomas, D. A. and Carrell, R. W. A protein structural approach to the
solution of biological problems: á1-antitrypsin as a recent example. Am. J.
Physiol. 165 (Lung Cell. Mol. Physiol. 9), L211-L219. 1993
Lynmarie, K. and Thompson. K Unraveling the secrets of Alzheimer’s
â-amyloid fibrils. Proc. Natl. Acad. Sci. 100, 383-385. 2003
Lirkotadze, M. D., Condron, M. M. and Teplow, D., B. Identification and
characterization of key kinetic intermediates in amyloid â-protein
fibrillogenesis. J. Mol. Biol. 312, 1103-1119. 2001
Mast, A. E., Engild, J. J., Pizzo, S. V., and Salvesen, G. Analysis of the
plasma elimination kinetics and conformational stabilities of native,
proteinase-complexed, and reactive site cleaved serpins: Comparison of
á1-antiplasmin, angiotensinogen, and ovalbumin. Biochemistry 30,
1723-1730. 1991
Maury, C. P. Reactive (secondary) amyloidosis and its pathogenesis.
Rheunatol. Int. 5, 1-7. 1984
Murphy, R. M. Peptide aggregation in neurodegenerative disease. Annu.
Rev. Biomed. Eng. 4, 155-174. 2002
Yamada, N., Ariga, K., Naito, M., Matsubara, K. and Koyama. E.
Regulation of â-sheet structures within amyloid-like â-sheet assemblage
from tripeptide derivatives J. Am. Chem. Soc. 120, 12192 -12199, 1998
Pemberton, P. A., Stein, P. E., Pepys, M. B., Potter, J. M., Carrell, R.
W.and Baltz, M. L. Hormone binding globulins undergo serpin
conformational change in inflammation. Nature 336, 257-258. 1983
Pepys, M. B., and Baltz, M. L. Acute phase proteins with special
references to C-reactive protein and related proteins (pentraxins) and
serum amyloid A component. Adv. Immunol. 34, 141-212. 1983
Perlmutter, D. H., Joslin, G., Nelson, P., Schasteen, C., Adams, S. P. and
Fallon, R. J. Endocytosis and degradation of alpha-1-antitrypsin
complexes is mediated by the serpin-enzyme complex (SEC) receptor. J.
Biol. Chem. 265, 16713-16716. 1990
Potempa, J., Korzus, E., and Travis, J. The serpin superfamily of
proteinase inhibitors: Structure, function, and regulation. J. Biol. Chem.
23, 15957-15960. 1994
Provencher, T. and Glockner, M. The fractions of secondary structures
from the contin method. Biochemistry 20, 33-37. 1981 Program Modified
by Sreerama. N. 1999
Rochet, J. C. and Lansbury, P. T. Amyloid fibrillogenesis: theme and
variations. Curr. Opin. Struct. Biol. 10, 60-68. 2000
Ryu, S. E., Choi, H. J., Kwon, K. S., Lee, K. N. and Yu, M. H. The native
strain in the hydrophobic core and flexible reactive loop of a serine
protease inhibitor: Crystal structure of an uncleaved alpha1-antitrypsin at
2.7 Å, Structure 4, 1181-1192. 1996
Selkoe, D. J. Normal and abnormal biology of the â-amyloid precursor
protein . Annu. Rev. Neurosci. 17, 489-517. 1994
Serpell, L. C. Alzheimer’s amyloid fibrils: structure and assembly,
Biochim. Biophys. Acta 1505, 16-30. 2000
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer. C, Cai,
X. D., McKay, D. M., Tintner, R., Frangione, B., and Younkin, S. G.
Production of the Alzheimer amyloid â protein by normal proteolytic
processing. Science 258, 126-135. 1992
Snow, A. D., Sekiguchi, R. T., Nochlin, D., Kalaria, R. N., and Kimata, K.
Heparan sulfate proteoglycan in diffuse plaques of hippocampus but not
of cerebellum in Alzheimer’s disease brain. Am. J. Pathol. 144, 337-347.
1994
Spencer, R. G. S., Halverson, K. J., Auger, M., McDermoyy, A. E.,
Griffin, R. G. and Lanxbury, P. T., Jr. An unusual peptide conformation
may precipitate amyloid formation in Alzheimer’s disease: Application of
solid-state NMR to the determination of protein secondary structure.
Biochemistry 30, 10328-10387. 1991
Stone, M. J. Amyloidosis: A final common pathway for protein
deposition in tissue. Blood 75, 531-545. 1990
Sticht, H., Bayer, P., Willbold, D., Dames, S., Hilbich, C., Beyreuther, K.,
Frank, R. W., and Rosch, P. Eur. J. Biochem. 233, 293-298. 1995
Soto, C. Protein misfolding and disease; protein refolding and therapy.
FEBS Lett.. 498, 204-207. 2001
Sreerama, T. and Woody, M. The fractions of secondary structures from
the self-consistent method. Anal. Biochem. 209, 32. 1993
Sreerama, T. and Woody, M. The fractions of secondary structures from
the self-consistent method. Protein Science 8, 370-380. 1999
Uversky, V. N., Li, J and Fink, A. L. Evidence for a partially folded
intermediate in á-synuclein fibril formation. J. Biol. Chem. 276,
10737-10744. 2001
Venyaminov, S. Y. and Vassilenko, K. S. Detremination of protein tertiary
structure class from circular dichroism spectra, Anal. Biochem. 222,
176-184. 1994
Walsh, D. M., Harley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M.,
Lomakin, A., Benedek, G. B., Selkoe, D. J., and Teplow, D. B. Amyloid
â-protein fibrillogenesis Structure and biological activity of protofibrillar
intermediates. J. Biol. Chem. 274, 25945-25952. 1990
Weisgraber, K. H., Pitas, R. E., and Mahlay, R.W. Lipoproteins,
neurobiology, and Alzheimer’s disease: Structure and function of
apolipoprotein E. Curr. Opin. Struct. Biol. 4, 507-515. 1994
Young, J. K., Anklin, C., Hicks, R. P. Nuclear magnetic resonance and
molecular modeling investigations of the neuropeptide substance P in the
presence of 15 mM sodium dodecyl sulfate micelles. Biopolymers 34,
1449-1462. 1994
Zagorski, M. G., and Barrow, C. J. NMR studies of amyloid beta-peptides:
proton assignments, secondary structure, and mechanism of an
alpha-helix and beta-sheet conversion for a homologous, 28-residue,
N-terminal fragment. Biochemistry 31, 5621-5631. 1992
Zerovnik, E. Amyloid-fibril formation Proposed mechanisms and
relevance to conformational disease. Eur. J, Bio. 269, 3362 -3374.2002
Zerovnik, E., Pompe-Novak, M., Škatabot, M., Ravikar, M., Musevic, I.
and Turk, V. Human stefin B readily forms amyloid fibrils in vivo.
Biochem. Biophys. Acta 1595, 1-5. 2002
Zhu, M., Souillac, P. O., Ionescu-Zanetti, C., Cater, S. A., and Fink,A. L.
Surface-catalyzed amyloid fibril formation. J. Biol. Chem. 277,
50914-50922. 2002
Wüthrich, K. NMR of proteins and nucleic acids. Wiley-Interscience
Publish. Switzerland. p.17. 1986.
黃忠智及余靖,利用核磁共振光譜決定台灣眼鏡蛇蛇毒蛋白分子的水溶液中三度空間結構。科儀新知第十五卷,第六期, 21-39, 1994。
陳金榜, 蛋白質在水溶液中之結構—多維異核核磁共振之應用。科儀
新知第十五卷,第六期, 40-46, 1994。
周立哲,馬來腹蛇蛇毒蛋白及其D51E 突變蛋白結構的核磁共振研
究。國立成功大學生物化學研究所碩士論文,2000。
劉沛棻,利用核磁共振光譜決定間白素分子(ILF)和酸結合區的水
溶液中三度空間結構。國立成功大學生物化學研究所碩士論文,2001。
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔