---
_id: '1566'
abstract:
- lang: eng
  text: Deposits 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.
acknowledgement: 'We acknowledge the support by the EU Joint Programme in Neurodegenerative
  Diseases (JPND AC14/00037) project. The project is supported through the following
  funding organisations under the aegis of JPND—www.jpnd.eu: Ireland, HRB; Poland,
  National Science Centre; and Spain, ISCIII. '
article_number: e1004541
article_processing_charge: No
author:
- first_name: Àngel
  full_name: Gómez Sicilia, Àngel
  last_name: Gómez Sicilia
- first_name: Mateusz K
  full_name: Sikora, Mateusz K
  id: 2F74BCDE-F248-11E8-B48F-1D18A9856A87
  last_name: Sikora
- first_name: Marek
  full_name: Cieplak, Marek
  last_name: Cieplak
- first_name: Mariano
  full_name: Carrión Vázquez, Mariano
  last_name: Carrión Vázquez
citation:
  ama: Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. An exploration of
    the universe of polyglutamine structures. <i>PLoS Computational Biology</i>. 2015;11(10).
    doi:<a href="https://doi.org/10.1371/journal.pcbi.1004541">10.1371/journal.pcbi.1004541</a>
  apa: Gómez Sicilia, À., Sikora, M. K., Cieplak, M., &#38; Carrión Vázquez, M. (2015).
    An exploration of the universe of polyglutamine structures. <i>PLoS Computational
    Biology</i>. Public Library of Science. <a href="https://doi.org/10.1371/journal.pcbi.1004541">https://doi.org/10.1371/journal.pcbi.1004541</a>
  chicago: Gómez Sicilia, Àngel, Mateusz K Sikora, Marek Cieplak, and Mariano Carrión
    Vázquez. “An Exploration of the Universe of Polyglutamine Structures.” <i>PLoS
    Computational Biology</i>. Public Library of Science, 2015. <a href="https://doi.org/10.1371/journal.pcbi.1004541">https://doi.org/10.1371/journal.pcbi.1004541</a>.
  ieee: À. Gómez Sicilia, M. K. Sikora, M. Cieplak, and M. Carrión Vázquez, “An exploration
    of the universe of polyglutamine structures,” <i>PLoS Computational Biology</i>,
    vol. 11, no. 10. Public Library of Science, 2015.
  ista: Gómez Sicilia À, Sikora MK, Cieplak M, Carrión Vázquez M. 2015. An exploration
    of the universe of polyglutamine structures. PLoS Computational Biology. 11(10),
    e1004541.
  mla: Gómez Sicilia, Àngel, et al. “An Exploration of the Universe of Polyglutamine
    Structures.” <i>PLoS Computational Biology</i>, vol. 11, no. 10, e1004541, Public
    Library of Science, 2015, doi:<a href="https://doi.org/10.1371/journal.pcbi.1004541">10.1371/journal.pcbi.1004541</a>.
  short: À. Gómez Sicilia, M.K. Sikora, M. Cieplak, M. Carrión Vázquez, PLoS Computational
    Biology 11 (2015).
date_created: 2018-12-11T11:52:45Z
date_published: 2015-10-23T00:00:00Z
date_updated: 2026-07-06T13:54:28Z
day: '23'
ddc:
- '570'
department:
- _id: CaHe
doi: 10.1371/journal.pcbi.1004541
external_id:
  isi:
  - '000364399700067'
file:
- access_level: open_access
  checksum: 8b67d729be663bfc9af04bfd94459655
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:16:21Z
  date_updated: 2020-07-14T12:45:02Z
  file_id: '5207'
  file_name: IST-2016-478-v1+1_journal.pcbi.1004541.pdf
  file_size: 1412511
  relation: main_file
file_date_updated: 2020-07-14T12:45:02Z
has_accepted_license: '1'
intvolume: '        11'
isi: 1
issue: '10'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
publication: PLoS Computational Biology
publication_status: published
publisher: Public Library of Science
publist_id: '5605'
pubrep_id: '478'
quality_controlled: '1'
related_material:
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  - id: '9714'
    relation: research_data
    status: public
scopus_import: '1'
status: public
title: An exploration of the universe of polyglutamine structures
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 11
year: '2015'
...