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

FEBS Letters

Sharma, Deepak¹  Pasha, Santosh¹  Sharma, Sunita¹  Brahmachari, Samir K¹ 

[1] Functional Genomics Unit, Centre for Biochemical Technology, Delhi University Campus, Mall Road, Delhi 110007, India

关键词: Polyglutamine;    Insolubility;    SCA1;    β-Sheet;    Aggregation;    Neurodegenerative disease;    Circular dichroism;   

DOI  :  10.1016/S0014-5793(99)00933-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown