Amyloid fibrils are proteinaceous aggregates that can be formed in the process of degenerative diseases, such as Alzheimer’s and Creutzfeldt-Jakob diseases. The process of fibril formation can also be observed, under appropriate conditions, in many proteins not involved in neurodegenerative diseases. Insulin, a peptide hormone consisting of two polypeptides linked together by two interchain and one intrachain disulfide bonds, is a model of fibril formation that has produced a wealth of biochemical and structural data making it an excellent model for amyloid studies. Insulin from different mammal species, such as human recombinant, bovine and porcine, has small differences in sequence that produce variations in the three-dimensional structure. Infrared spectroscopy, although it is not a high-resolution technique, it presents the advantages of fast-time response and wider applicability required for studying aggregated materials. The time-course of fibril formation can be followed looking at the appearance of a characteristic band in the region of β-sheet structure. Human insulin, with a different aminoacid in the Nterminal segment, has a lower time in fibril formation than bovine or porcine. The wavenumber and the percentage of the band corresponding to the fibril is different in bovine as compared with human and porcine insulin, what is associated with a change in aminoacids 8 and 10 located in the intrachain disulfide bond. The results show that even if the macromolecular structure of the fibrils is alike, the process is different depending on small changes in protein sequence.
Keywords: Amyloid, Fibrils, Infrared spectroscopy, Insulin, Protein structure
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de la Arada, I., Arrondo, J.L.R. (2007). An Infrared Study of Fibril Formation in Insulin from Different Sources. In: Pifat-Mrzljak, G. (eds) Supramolecular Structure and Function 9. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6466-1_2
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