Bacterial expression, purification, and functional mapping of the amyloid beta/A4 protein precursor.

作者: J M Roch , I P Shapiro , M P Sundsmo , D A Otero , L M Refolo

DOI: 10.1016/S0021-9258(18)45864-4

关键词: Binding sitePeptideProtease inhibitor (biology)BiologyAmino acidPeptide sequenceActive siteProtein precursorBiochemistryAmyloid beta

摘要: The secreted form of Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in cell growth regulation (Saitoh, T., Sundsmo, M., Roch, J.-M., Kimura, N., Cole, G., Schubert, D., Oltersdorf, and Schenk, D.B. (1989) Cell 58, 615-622). Using a strong prokaryotic expression system, we expressed, Escherichia coli, peptide fragments covering different regions the APP-695. longest these (KB75, 572 amino acids from Val-20 Ile-591), which contained neither Kunitz-type protease inhibitor (KPI) domain nor beta/A4-protein domain, was purified biologically active terms regulation. Two other APP (KB48, 316 Met-335; RB17, 150 Thr-296 Pro-445), overlapping by only 40 at close site C-terminal KPI insertion site, were also active. Furthermore, chemically synthesized 40-residue corresponding this region overlap stimulated A-1 fibroblasts. These results establish presence growth-promoting activity APP-695 suggest that lies within 40-amino acid next site.

参考文章(55)
R. Smith, D. Higuchi, G. Broze, Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein. Science. ,vol. 248, pp. 1126- 1128 ,(1990) , 10.1126/SCIENCE.2111585
D. Schubert, L-W. Jin, T. Saitoh, Greg Cole, The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion Neuron. ,vol. 3, pp. 689- 694 ,(1989) , 10.1016/0896-6273(89)90237-7
H.M. Krisch, A. Bolle, R.H. Epstein, Regulation of the synthesis of bacteriophage T4 gene 32 protein. Journal of Molecular Biology. ,vol. 88, pp. 89- 104 ,(1974) , 10.1016/0022-2836(74)90296-4
Jie Kang, Hans-Georg Lemaire, Axel Unterbeck, J. Michael Salbaum, Colin L. Masters, Karl-Heinz Grzeschik, Gerd Multhaup, Konrad Beyreuther, Benno Müller-Hill, The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor Nature. ,vol. 325, pp. 733- 736 ,(1987) , 10.1038/325733A0
E. H. Koo, S. S. Sisodia, D. R. Archer, L. J. Martin, A. Weidemann, K. Beyreuther, P. Fischer, C. L. Masters, D. L. Price, Precursor of amyloid protein in Alzheimer disease undergoes fast anterograde axonal transport. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 87, pp. 1561- 1565 ,(1990) , 10.1073/PNAS.87.4.1561
Andreas Weidemann, Gerhard König, Dirk Bunke, Peter Fischer, J.Michael Salbaum, Colin L. Masters, Konrad Beyreuther, Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein Cell. ,vol. 57, pp. 115- 126 ,(1989) , 10.1016/0092-8674(89)90177-3
B. A. Yankner, A. Caceres, L. K. Duffy, Nerve growth factor potentiates the neurotoxicity of beta amyloid. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 87, pp. 9020- 9023 ,(1990) , 10.1073/PNAS.87.22.9020
N. K. Robakis, N. Ramakrishna, G. Wolfe, H. M. Wisniewski, Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 84, pp. 4190- 4194 ,(1987) , 10.1073/PNAS.84.12.4190
D Goldgaber, M. Lerman, O. McBride, U Saffiotti, D. Gajdusek, Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease Science. ,vol. 235, pp. 877- 880 ,(1987) , 10.1126/SCIENCE.3810169