Abstract
Expansion of polyglutamine (polyQ) sequence in some proteins leads to their aggregation, which is responsible for neurodegenerative diseases like Huntington’s disease, ataxia etc. A flanking domain is usually fused at the N-terminal to polyQ in these proteins. On linking the flanking residues to polyQ, they accelerate aggregation of the proteins, which initiates from the flanking residues. In this report the inherent propensity of the flanking residues towards aggregation in six aggregating proteins has been elucidated from their primary sequences with the help of Betascan and PASTA programs and explored unambiguously. This will provide a molecular mechanism of this process. Suppression of aggregation using chaperones like αB-crystallin by masking the exposed hydrophobic surface of flanking residues is also documented through molecular docking, which could be applied for inhibition of aggregation of this type of proteins.
Keywords: PolyQ aggregation, flanking residues, chaperone
Protein & Peptide Letters
Title:Inherent Aggregation Propensity of Flanking Residues Attached to Polyglutamines: Implication to Aggregation Inhibition
Volume: 20 Issue: 5
Author(s): Kalyan Sundar Ghosh
Affiliation:
Keywords: PolyQ aggregation, flanking residues, chaperone
Abstract: Expansion of polyglutamine (polyQ) sequence in some proteins leads to their aggregation, which is responsible for neurodegenerative diseases like Huntington’s disease, ataxia etc. A flanking domain is usually fused at the N-terminal to polyQ in these proteins. On linking the flanking residues to polyQ, they accelerate aggregation of the proteins, which initiates from the flanking residues. In this report the inherent propensity of the flanking residues towards aggregation in six aggregating proteins has been elucidated from their primary sequences with the help of Betascan and PASTA programs and explored unambiguously. This will provide a molecular mechanism of this process. Suppression of aggregation using chaperones like αB-crystallin by masking the exposed hydrophobic surface of flanking residues is also documented through molecular docking, which could be applied for inhibition of aggregation of this type of proteins.
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Cite this article as:
Sundar Ghosh Kalyan, Inherent Aggregation Propensity of Flanking Residues Attached to Polyglutamines: Implication to Aggregation Inhibition, Protein & Peptide Letters 2013; 20 (5) . https://dx.doi.org/10.2174/0929866511320050010
DOI https://dx.doi.org/10.2174/0929866511320050010 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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