cytochrome-c-t and Amyloidosis

Protein folding is a natural phenomenon through which a linear polypeptide possessing necessary information attains three-dimension functionally active conformation. This is a complex and multistep process and therefore, the presence of several intermediary structures could be speculated as a result of protein folding. In in vivo, this folding process is governed by the assistance of other proteins called molecular chaperones and heat shock proteins. Due to the mechanism of protein folding, these intermediary structures remain major challenge for modern biology. Mutation in gene encoding amino acid can cause adverse environmental conditions which may result in misfolding of the linear polypeptide followed by the formation of aggregates and amyloidosis. Aggregation contributes to the pathophysiology of several maladies including diabetes mellitus, Huntington's and Alzheimer's disease. The propensity of native structure to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. During aggregation of a protein, transition from α helix to β sheet is observed, and mainly β sheeted structure is visualised in a mature fibril. Heme proteins are very crucial for major life activities like transport of oxygen and carbon dioxide, synthesis of ATP, role in electron transport chain, and detoxification of free radicals formed during biochemical reactions. Any structural variation in the heme proteins may lead to a fatal response. Hence characterization of the folding intermediates becomes crucial. The characterization has been deciphered with the help of strong denaturants like acetonitrile and TFE. Moreover, possible role of elimination of these aggregates and prevention of protein denaturation is also discussed. Current review deals with the basic process and mechanism of the protein folding in general and the ultimate outcomes of the protein misfolding. Since Native conformation of heme proteins is essential for some vital activities as listed above, we have discussed possible prevention of denaturation and aggregation of heme proteins such as Hb, cyt c, catalase & peroxidase.

Topics: Alzheimer Disease; Amyloid; Amyloidosis; Catalase; Cytochromes c; Diabetes Mellitus; Gene Expression; Heat-Shock Proteins; Hemoglobins; Humans; Huntington Disease; Molecular Chaperones; Peroxidase; Protein Aggregates; Protein Conformation; Protein Folding

The question of how an aggregating protein can influence aggregation of other proteins located in its vicinity is particularly significant because many proteins coexist in cells. We demonstrate in vitro coaggregation and cross-seeding of lysozyme, bovine serum albumin, insulin, and cytochrome c during their amyloid formation. The coaggregation process seems to be more dependent on the temperature-induced intermediate species of these proteins and less dependent on their sequence identities. Because amyloid-linked inclusions and plaques are recognized as multicomponent entities originating from aggregation of the associated protein, these findings may add new insights into the mechanistic understanding of amyloid-related pathologies.

Topics: Amino Acid Sequence; Amyloid; Amyloidosis; Animals; Cattle; Circular Dichroism; Cytochromes c; Humans; Insulin; Kinetics; Microscopy, Electron, Transmission; Molecular Sequence Data; Muramidase; Protein Aggregates; Protein Aggregation, Pathological; Sequence Homology, Amino Acid; Serum Albumin, Bovine; Spectrometry, Fluorescence