Surin, AK., et al. Identification of Amyloidogenic Regions in the Spine of Insulin Fibrils. 84(1) 47-55

To reveal conformational changes resulting in the formation of insulin fibrils, it is necessary to identify amyloidogenic regions in the structure of protein monomers. Different models of insulin fibrillogenesis have been proposed previously. However, precise regions responsible for the formation of amyloid fibrils have not been identified. Using bioinformatics programs for predicting amyloidogenic regions, we have determined some common amyloidogenic sequences in the structure of insulin monomers. The use of limited proteolysis and mass spectrometry analysis of the obtained protein fragments resistant to the action of proteases allowed us to identify amino acid sequences in the insulin structure that can form the spine of the insulin fibrils. The obtained results are in agreement with the earlier proposed model of fibril formation from the ring-like oligomers and can be used for designing insulin analogs resistant to amyloidogenesis.