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Peptide models for inherited neurodegenerative disorders: conformation and aggregation properties of long polyglutamine peptides with and without interruptions
Author(s) -
Sharma Deepak,
Sharma Sunita,
Pasha Santosh,
Brahmachari Samir K
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00933-3
Subject(s) - glutamine , histidine , random coil , ataxia , peptide , neurodegeneration , chemistry , biochemistry , biophysics , neuroscience , amino acid , biology , medicine , protein secondary structure , disease
Several neurodegenerative diseases are caused by expansion of polyglutamine repeats in the affected proteins. In spino‐cerebellar ataxia type 1 (SCA1), histidine interruptions have been reported to mitigate the pathological effects of long glutamine stretches. To understand this phenomenon, we investigated the conformational preferences of peptides containing both the uninterrupted polyglutamine stretches and those with histidine interruption(s) as seen in SCA1 normals. Our study suggests that substitution of histidines by glutamines induces a conformational change which results in decreased solubility and increased aggregation. Our findings also suggest that all the polyglutamine peptides with and without interruption(s) adopt a β‐structure and not random coil.