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Osmolytes modulate polyglutamine aggregation in a sequence dependent manner
Author(s) -
Saha Itika,
Singh Virender,
Burra Gunasekhar,
Thakur Ashwani Kumar
Publication year - 2018
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.3115
Subject(s) - osmolyte , chemistry , protein aggregation , trehalose , biochemistry , osmoprotectant , trimethylamine , biophysics , arginine , betaine , phenylethanoid , methylamines , glutamine , amino acid , biology , proline , stereochemistry , glycoside , catalysis
Osmolytes stabilize protein structure and suppress protein aggregation. The mechanism of how osmolytes impact polyglutamine (polyQ) aggregation implicated in Huntington's disease was studied. By using a reverse‐phase chromatography assay, we show that methylamines‐trimethylamine N‐oxide and betaine are generic in enhancing polyQ aggregation, while a disaccharide trehalose and an amino acid citrulline moderately retard polyQ aggregation in a sequence specific manner. Despite the altered kinetics, the fundamental nucleation mechanism of polyQ aggregation and the nature of end stage aggregates remains unaffected. These results highlight the importance of using osmolytes as modulatory agents of polyQ aggregation.