English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/153611
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

An Exploration of the Universe of Polyglutamine Structures

AuthorsGómez-Sicilia, Ángel ; Sikora, M.; Cieplak, Marek; Carrión-Vázquez, Mariano Sixto
KeywordsProteins
Issue Date2015
PublisherPublic Library of Science
CitationPLoS Computational Biology 11 (2015)
AbstractDeposits of misfolded proteins in the human brain are associated with the development of many neurodegenerative diseases. Recent studies show that these proteins have common traits even at the monomer level. Among them, a polyglutamine region that is present in huntingtin is known to exhibit a correlation between the length of the chain and the severity as well as the earliness of the onset of Huntington disease. Here, we apply bias exchange molecular dynamics to generate structures of polyglutamine expansions of several lengths and characterize the resulting independent conformations. We compare the properties of these conformations to those of the standard proteins, as well as to other homopolymeric tracts. We find that, similar to the previously studied polyvaline chains, the set of possible transient folds is much broader than the set of known-to-date folds, although the conformations have different structures. We show that the mechanical stability is not related to any simple geometrical characteristics of the structures. We demonstrate that long polyglutamine expansions result in higher mechanical stability than the shorter ones. They also have a longer life span and are substantially more prone to form knotted structures. The knotted region has an average length of 35 residues, similar to the typical threshold for most polyglutamine-related diseases. Similarly, changes in shape and mechanical stability appear once the total length of the peptide exceeds this threshold of 35 glutamine residues. We suggest that knotted conformers may also harm the cellular machinery and thus lead to disease.
URIhttp://hdl.handle.net/10261/153611
DOI10.1371/journal.pcbi.1004541
Identifiersdoi: 10.1371/journal.pcbi.1004541
issn: 1553-7358
Appears in Collections:(IC) Artículos
Files in This Item:
File Description SizeFormat 
Plos Computationnal Biology.pdf1,38 MBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.