A stable G-quartet binds to a huntingtin protein fragment containing expanded polyglutamine tracks. Yerkes, S., Vesenka, J., & Kmiec, E. B C. - 1. Journal of Neuroscience Research, 88(2):335–345 ST – A stable G–quartet binds to a huntin, 2010. tex.city: Department of Biological Science, University of Delaware, Newark, Delaware; Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, West Virginia; Department of Chemistry and Physics, University of New England, Biddeford, Maine![A stable G-quartet binds to a huntingtin protein fragment containing expanded polyglutamine tracks [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Huntington's disease (HD) is a progressive neurodegenerative disorder that is inherited in an autosomal dominant fashion. The disease is the result of an expanded CAG repeat in exon 1 of the HD gene, which encodes an elongated polyglutamine tract in the mutant form of the protein, huntingtin. Disease pathogenesis is linked to intracellular aggregates that form because of the tendency of the mutant protein to misfold. The role of huntingtin aggregates in disease pathology is unclear; it has been proposed that the aggregates themselves are toxic because of their ability to sequester intracellular proteins and disrupt normal cellular function. In addition, the mechanistic steps that lead to aggregate formation appear to be central to HD pathology. We have previously reported that guanosine-rich oligonucleotides with the ability to fold into a G-quartet are effective inhibitors of the aggregation process of a huntingtin protein fragment with an elongated polyglutamine tract, Htn 1-171(Q58). The most active molecule is composed of 20 guanosine residues, which adopt a G-wire conformation. Here we establish that G20 inhibits protein aggregation as judged by native gel electrophoresis, an agarose gel electrophoresis for resolving aggregates (AGERA) assay, and an immunoblotting assay. We also visualize the G20-Htn1-171(Q58) protein complex by using a streptavidin-biotin pull-down assay as well as atomic force microscopy (AFM). The G20 molecule also interacts with Htn1-171(Q23), a fusion protein that contains 23 glutamine residues instead of 58 (Q58), but in a more degenerate and nonspecific fashion. Taken together, our data support the notion that G20 exhibits some selectivity in binding to specific protein species that assemble along the aggregation pathway. © 2009 Wiley-Liss, Inc.
@article{Yerkes2010,
title = {A stable {G}-quartet binds to a huntingtin protein fragment containing expanded polyglutamine tracks},
volume = {88},
issn = {1097-4547},
url = {http://dx.doi.org/10.1002/jnr.22210},
doi = {10.1002/jnr.22210},
abstract = {Huntington's disease (HD) is a progressive neurodegenerative disorder that is inherited in an autosomal dominant fashion. The disease is the result of an expanded CAG repeat in exon 1 of the HD gene, which encodes an elongated polyglutamine tract in the mutant form of the protein, huntingtin. Disease pathogenesis is linked to intracellular aggregates that form because of the tendency of the mutant protein to misfold. The role of huntingtin aggregates in disease pathology is unclear; it has been proposed that the aggregates themselves are toxic because of their ability to sequester intracellular proteins and disrupt normal cellular function. In addition, the mechanistic steps that lead to aggregate formation appear to be central to HD pathology. We have previously reported that guanosine-rich oligonucleotides with the ability to fold into a G-quartet are effective inhibitors of the aggregation process of a huntingtin protein fragment with an elongated polyglutamine tract, Htn 1-171(Q58). The most active molecule is composed of 20 guanosine residues, which adopt a G-wire conformation. Here we establish that G20 inhibits protein aggregation as judged by native gel electrophoresis, an agarose gel electrophoresis for resolving aggregates (AGERA) assay, and an immunoblotting assay. We also visualize the G20-Htn1-171(Q58) protein complex by using a streptavidin-biotin pull-down assay as well as atomic force microscopy (AFM). The G20 molecule also interacts with Htn1-171(Q23), a fusion protein that contains 23 glutamine residues instead of 58 (Q58), but in a more degenerate and nonspecific fashion. Taken together, our data support the notion that G20 exhibits some selectivity in binding to specific protein species that assemble along the aggregation pathway. © 2009 Wiley-Liss, Inc.},
number = {2},
journal = {Journal of Neuroscience Research},
author = {Yerkes, Sarah and Vesenka, James and Kmiec, Eric B C1 - 10.1002/jnr.22210},
year = {2010},
note = {tex.city: Department of Biological Science, University of Delaware, Newark, Delaware; Marshall Institute for Interdisciplinary Research, Marshall University, Huntington, West Virginia; Department of Chemistry and Physics, University of New England, Biddeford, Maine},
keywords = {\#nosource},
pages = {335--345 ST -- A stable G--quartet binds to a huntin},
}
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