Peptide models for inherited neurodegenerative disorders: conformation andaggregation properties of long polyglutamine peptides with and without interruptions

Several neurodegenerative diseases are caused by expansion of polyglutamine repeats in the affected proteins. In spine-cerebellar ataxia type 1 (SCA1) , histidine interruptions have been reported to mitigate the pathological e ffects of long glutamine stretches. To understand this phenomenon, we inves tigated the conformational preferences of peptides containing both the unin terrupted 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 s olubility and increased aggregation, Our findings also suggest that all the polyglutamine peptides with and without interruption(s) adopt a beta-struc ture and not random coil. (C) 1999 Federation of European Biochemical Socie ties.