Title:Process, Outcomes and Possible Elimination of Aggregation with Special Reference to Heme Proteins; Likely Remediations of Proteinopathies
Volume: 21
Issue: 6
Author(s): Mohammad Furkan and Rizwan Hasan Khan*
Affiliation:
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University Aligarh, UP, 202002,India
Keywords:
Aggregation, amyloid inhibitors, anthroquinone, heme proteins, neurodegenerative diseases, polyphenols.
Abstract: 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.
