AP/MALDI-MS complete characterization of the proteolytic fragments produced by the interaction of insulin degrading enzyme with bovine insulin(511 views) Grasso G, Rizzarelli E, Spoto G
J Mass Spectrom (ISSN: 1076-5174, 1096-9888), 2007 Dec; 42(12): 1590-1598.
Keywords: Alkylation, Insulin, Maldi, Reduction, Mass Spectrometry, Peptides, Proteolysis, Substrates, Bovine Insulin, Cleavage Sites, Proteolytic Fragments, Enzyme Activity, Insulinase, Peptide Fragment, Conference Paper, Enzyme Degradation, Matrix Assisted Laser Desorption Ionization Time Of Flight Mass Spectrometry, Priority Journal, Protein Aggregation, Protein Degradation, Protein Interaction, Reproducibility, Screening, Amino Acid Sequence, Animals, Cattle, Cells, Cultured, Insulysin, Molecular Sequence Data, Matrix-Assisted Laser Desorption-Ionization, Spodoptera,
Affiliations: *** IBB - CNR ***
Dipartimento di Scienze Chimiche, Universita di Catania, Viale Andrea Doria 6, 95125, Catania, Italy. grassog@unict.it
Istituto Biostrutture e Bioimmagini, CNR, Viale A. Doria 6, Catania, Italy
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Duckworth, W. C., Insulin degradation: Mechanisms, products, and significance (1988) Endocrine Revieivs, 9, p. 319
Gehm, B. D., Rosner, M. R., Regulation of insulin, epidermal growth factor, and transforming growth factor-alpha levels by growth factor-degrading enzymes (1991) Endocrinology, 128, p. 1603
Kuo, W. L., Gehm, B. D., Rosner, M. R., Regulation of insulin degradation: Expression of an evolutionarily conserved insulin-degrading enzyme increases degradation via an intracellular pathway (1991) Molecular Endocrinology, 5, p. 1467
Kurochkin, I. V., Insulin-degrading enzyme: Embarking on amyloid destruction (2001) Trends in Biochemical Sciences, 26, p. 421
Blomqvist, M. E. -L., Silburn, P. A., Buchanan, D. D., Andreasen, N., Blennow, K., Pedersen, N. L., Brookes, A. J., Prince, J. A., Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease (2004) Neurogenetics, 5, p. 115
Kurochkin, I. V., Goto, S., Alzheimer's -amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme (1994) FEBS Letters, 345, p. 33
Kurochkin, I. V., Amyloidogenic determinant as a substrate recognition motif of insulin-degrading enzyme (1998) FEBS Letters, 427, p. 153
Muir, A. V., Offord, R. E., Davies, J. G., The identification of a major product of the degradation of insulin by 'Insulin proteinase' (1986) Biochemical Journal, 237, p. 631
Davies, J. G., Muir, A. V., Offord, R. E., Identification of some cleavage sites of insulin by insulin proteinase (1986) Biochemical Journal, 240, p. 609
Vu, L., St cklin, R., Rose, K., Offord, R. E., Facile identification by electrospray mass spectrometry of the insulin fragment A14-21 - B17-30 produced by insulin proteinase (1993) Rapid Communications in Mass Spectrometry, 7, p. 1048
Savoy, L. A., Jones, R. M. L., Pochon, S., Davies, G., Muir, A. V., Offord, R. E., Rose, K. B., Identification by fast atom bombardment mass spectrometry of insulin fragments produced by insulin proteinase (1988) Biochemical Journal, 249, p. 215
Duckworth, W. C., Bennett, R. G., Hamel, F. G., Insulin degradation: Progress and potential (1998) Endocrine Revieivs, 19, p. 608
Duckworth, W. C., Garcia, J. V., Liepnieks, J. J., Hamel, F. G., Hermodson, M. A., Frank, B. H., Rosner, M. R., Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites (1989) Biochemistry, 28, p. 2471
Hong, D. -P., Ahmad, A., Fink, A. L., Fibrillation of human insulin A and B chains (2006) Biochemistry, 45, p. 9342
Nettleton, E. J., Tito, P., Sunde, M., Bouchard, M., Dobson, C. M., Robinson, C. V., Characterization of the oligomeric states of insulin in self-assembly and amyloid fibril formation by mass spectrometry (2000) Biophysical Journal, 79, p. 1053
Mehl, J. T., Cummings, J. J., Rohde, E., Yates, N. N., Automated protein identification using atmospheric-pressure matrix-assisted laser desorption/ionization (2003) Rapid Communications in Mass Spectrometry, 17, p. 1600
Creaser, C. S., Reynolds, J. C., Harvey, D. J., Structural analysis of oligosaccharides by atmospheric pressure matrix-assisted laser desorption/ionisation quadrupole ion trap mass spectrometry (2002) Rapid Communications in Mass Spectrometry, 16, p. 176
Moyer, S. C., Cotter, R. J., Woods, A. S., Fragmentation of phosphopeptides by atmospheric pressure MALDI and ESI/ion trap mass spectrometry (2002) Journal of the American Society for Mass Spectrometry, 13, p. 274
Tan, P. V., Laiko, W., Doroshenko, V. M., Atmospheric pressure MALDI with pulsed dynamic focusing for high-efficiency transmission of ions into a mass spectrometer (2004) Analytical Chemistry, 76, p. 2462
Schneider, B. B., Lock, C., Covey, T. R., AP and vacuum MALDI on a QqLIT instrument (2005) Journal of the American Society for Mass Spectrometry, 16, p. 176
Olsen, H. B., Ludvigsen, S., Kaarsholm, N. C., Solution structure of an engineered insulin monomer at neutral pH (1996) Biochemistry, 35, p. 8836
Farah, M. A., Bose, S., Lee, J. -H., Jung, H. -C., Kim, Y., Analysis of glycated insulin by MALDI-TOF mass spectrometry (2005) Biochimica et Biophysica Acta, 1725, p. 269
Song, E. S., Juliano, M. A., Juliano, L., Hersh, L. B., Substrate activation of insulin-degrading enzyme (insulysin): A potential target for drug development (2003) The Journal of Biological Chemistry, 278, p. 49789
Duckworth, W. C., Fawcett, J., Tsui, B. T., Bennett, R. G., Hamel, F. G., Biological activity of a fragment of insulin (2004) Biochemical and Biophysical Research Communications, 318, p. 1019
AP/MALDI-MS complete characterization of the proteolytic fragments produced by the interaction of insulin degrading enzyme with bovine insulin
The prominent role that insulin degrading enzyme (IDE) has in the clearance of insulin as well as of other molecules such as amyloid-beta has recently drawn much interest in the scientific community toward this protease. In order to give an insight into the manner of interaction of IDE with its substrates, several papers have focused on the structure of the IDE/insulin complex. In this scenario, although the cleavage sites involved in the interaction of insulin with IDE are known, a convenient experimental method that is able to identify in a complete and unambiguous way, all the peptide fragments generated by such interaction has yet to be found. MS-based experiments have often represented to be invaluable tools for the assessment of the cleavage sites, but the reported MS-spectra always show a partial coverage of all the peptide fragments generated by the enzyme interaction, lacking a complete characterization. In this work, we report a new experimental procedure by which an unambiguous as well as complete assignment of all the peptide fragments generated by the interaction of insulin with IDE is described. Atmospheric pressure/matrix-assisted laser desorption ionization (AP/MALDI) mass spectra are reported and the data recorded, together with the introduction of a reduction/alkylation step, allows us to fully characterize the cleavage sites of the bovine insulin interacting with IDE. Different experimental conditions are screened and some insights into the IDE/insulin system regarding preference of the cleavage and its dependence on particular experimental conditions used are also given. Investigation on the tendency that different insulin fragments have toward aggregation is also carried out. Good reproducibility, global and unambiguous assignment, low time-consuming experimental procedure, and requirements of enzyme in small amounts are some of the advantages of the proposed AP/MALDI based approach.
AP/MALDI-MS complete characterization of the proteolytic fragments produced by the interaction of insulin degrading enzyme with bovine insulin