Peptide models for inherited neurodegenerative disorders: conformation and aggregation properties of long polyglutamine peptides with and without interruptions.
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 beta-structure and not random coil.
Sharma
D
D
Functional Genomics Unit, Centre for Biochemical Technology, Delhi, India.
Sharma
S
S
Pasha
S
S
Brahmachari
S K
SK
D000067696:Ataxin-1; D000067528:Ataxins; D002942:Circular Dichroism; D006639:Histidine; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D011487:Protein Conformation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013132:Spinocerebellar Degenerations / Q000235:genetics
C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine; D006639:Histidine