دورية أكاديمية
F-actin binding regions on the androgen receptor and huntingtin increase aggregation and alter aggregate characteristics.
العنوان: | F-actin binding regions on the androgen receptor and huntingtin increase aggregation and alter aggregate characteristics. |
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المؤلفون: | Suzanne Angeli, Jieya Shao, Marc I Diamond |
المصدر: | PLoS ONE, Vol 5, Iss 2, p e9053 (2010) |
بيانات النشر: | Public Library of Science (PLoS), 2010. |
سنة النشر: | 2010 |
المجموعة: | LCC:Medicine LCC:Science |
مصطلحات موضوعية: | Medicine, Science |
الوصف: | Protein aggregation is associated with neurodegeneration. Polyglutamine expansion diseases such as spinobulbar muscular atrophy and Huntington disease feature proteins that are destabilized by an expanded polyglutamine tract in their N-termini. It has previously been reported that intracellular aggregation of these target proteins, the androgen receptor (AR) and huntingtin (Htt), is modulated by actin-regulatory pathways. Sequences that flank the polyglutamine tract of AR and Htt might influence protein aggregation and toxicity through protein-protein interactions, but this has not been studied in detail. Here we have evaluated an N-terminal 127 amino acid fragment of AR and Htt exon 1. The first 50 amino acids of ARN127 and the first 14 amino acids of Htt exon 1 mediate binding to filamentous actin in vitro. Deletion of these actin-binding regions renders the polyglutamine-expanded forms of ARN127 and Htt exon 1 less aggregation-prone, and increases the SDS-solubility of aggregates that do form. These regions thus appear to alter the aggregation frequency and type of polyglutamine-induced aggregation. These findings highlight the importance of flanking sequences in determining the propensity of unstable proteins to misfold. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1932-6203 |
Relation: | http://europepmc.org/articles/PMC2816219?pdf=render; https://doaj.org/toc/1932-6203 |
DOI: | 10.1371/journal.pone.0009053 |
URL الوصول: | https://doaj.org/article/d945fba450484987ab86ae214cd0b203 |
رقم الأكسشن: | edsdoj.945fba450484987ab86ae214cd0b203 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19326203 |
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DOI: | 10.1371/journal.pone.0009053 |