Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism

被引：0
|
作者：
Ashwani K Thakur
Murali Jayaraman
Rakesh Mishra
Monika Thakur
Veronique M Chellgren
In-Ja L Byeon
Dalaver H Anjum
Ravindra Kodali
Trevor P Creamer
James F Conway
Angela M Gronenborn
Ronald Wetzel
机构：
[1] Department of Structural Biology,Department of Molecular and Cellular Biochemistry
[2] Pittsburgh Institute for Neurodegenerative Diseases,undefined
[3] University of Pittsburgh School of Medicine,undefined
[4] University of Kentucky,undefined
来源：
Nature Structural & Molecular Biology | 2009年 / 16卷
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摘要：
The huntingtin protein (HTT) contains a polyQ tract preceded by an N-terminal flanking sequence (HTTNT) that contributes to HTT aggregation. Now the role of HTTNT in aggregation is explored in vitro, revealing a complex, multistep pathway initiated when polyQ disrupts HTTNT structure, enhancing the latter's assembly into prefibrillar aggregates. Within these intermediates, subsequent interactions of the polyQ moieties drive further assembly into compact amyloid aggregates.
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页码：380 / 389
页数：9
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