Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/99756
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Polyalanine expansions drive a shift into α-helical clusters without amyloid-fibril formation |
Other Titles: | Polyalanine expansions drive a shift into alpha-helical clusters without amyloid-fibril formation |
Author: | Polling, S. Ormsby, A. Wood, R. Lee, K. Shoubridge, C. Hughes, J. Thomas, P. Griffin, M. Hill, A. Bowden, Q. Böcking, T. Hatters, D. |
Citation: | Nature Structural and Molecular Biology, 2015; 22(12):1008-1015 |
Publisher: | Nature Publishing Group |
Issue Date: | 2015 |
ISSN: | 1545-9993 1545-9985 |
Statement of Responsibility: | Saskia Polling, Angelique R Ormsby, Rebecca J Wood, Kristie Lee, Cheryl Shoubridge, James N Hughes, Paul Q Thomas, Michael D W Griffin, Andrew F Hill, Quill Bowden, Till Böcking and Danny M Hatters |
Abstract: | Polyglutamine (polyGln) expansions in nine human proteins result in neurological diseases and induce the proteins' tendency to form β-rich amyloid fibrils and intracellular deposits. Less well known are at least nine other human diseases caused by polyalanine (polyAla)-expansion mutations in different proteins. The mechanisms of how polyAla aggregates under physiological conditions remain unclear and controversial. We show here that aggregation of polyAla is mechanistically dissimilar to that of polyGln and hence does not exhibit amyloid kinetics. PolyAla assembled spontaneously into α-helical clusters with diverse oligomeric states. Such clustering was pervasive in cells irrespective of visible aggregate formation, and it disrupted the normal physiological oligomeric state of two human proteins natively containing polyAla: ARX and SOX3. This self-assembly pattern indicates that polyAla expansions chronically disrupt protein behavior by imposing a deranged oligomeric status. |
Keywords: | Amyloid |
Description: | Published online 16 November 2015 |
Rights: | © 2015 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/nsmb.3127 |
Grant ID: | http://purl.org/au-research/grants/arc/DP120102763 http://purl.org/au-research/grants/arc/FT120100039 http://purl.org/au-research/grants/arc/FT100100411 http://purl.org/au-research/grants/arc/FT100100560 http://purl.org/au-research/grants/nhmrc/1049458 http://purl.org/au-research/grants/nhmrc/628946 http://purl.org/au-research/grants/nhmrc/465401 http://purl.org/au-research/grants/nhmrc/1049459 |
Published version: | http://dx.doi.org/10.1038/nsmb.3127 |
Appears in Collections: | Aurora harvest 3 Paediatrics publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.