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dc.contributor.author
Jung, Taeyang
dc.contributor.author
Shin, Baehyun
dc.contributor.author
Tamo, Giorgio
dc.contributor.author
Kim, Hyeongju
dc.contributor.author
Vijayvargia, Ravi
dc.contributor.author
Leitner, Alexander
dc.contributor.author
Marcaida, Maria J.
dc.contributor.author
Astorga-Wells, Juan
dc.contributor.author
Jung, Roy
dc.contributor.author
Aebersold, Ruedi
dc.contributor.author
Dal Peraro, Matteo
dc.contributor.author
Hebert, Hans
dc.contributor.author
Seong, Ihn Sik
dc.contributor.author
Sing, Ji-Joon
dc.date.accessioned
2021-07-15T07:15:12Z
dc.date.available
2020-09-04T20:18:06Z
dc.date.available
2020-09-10T13:20:52Z
dc.date.available
2021-01-07T15:11:24Z
dc.date.available
2021-01-08T09:50:52Z
dc.date.available
2021-07-15T07:15:12Z
dc.date.issued
2020-09-01
dc.identifier.issn
0969-2126
dc.identifier.issn
1878-4186
dc.identifier.other
10.1016/j.str.2020.06.008
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/438632
dc.identifier.doi
10.3929/ethz-b-000438632
dc.description.abstract
The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural information on its HEAT-repeat domains. Here, we present analyses of the impact of polyQ length on the structure and function of HTT via an integrative structural and biochemical approach. The cryo-EM analysis of normal (Q23) and disease (Q78) type HTTs shows that the structures of apo HTTs significantly differ from the structure of HTT in a HAP40 complex and that the polyQ expansion induces global structural changes in the relative movements among the HTT domains. In addition, we show that the polyQ expansion alters the phosphorylation pattern across HTT and that Ser2116 phosphorylation in turn affects the global structure and function of HTT. These results provide a molecular basis for the effect of the polyQ segment on HTT structure and activity, which may be important for HTT pathology.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Cell Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2020-07-14
ethz.journal.title
Structure
ethz.journal.volume
28
en_US
ethz.journal.issue
9
en_US
ethz.pages.start
1035
en_US
ethz.pages.end
1050
en_US
ethz.size
25 p. accepted version
en_US
ethz.version.deposit
acceptedVersion
en_US
ethz.grant
Proteomics 4D: The proteome in context
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Cambridge, MA
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf (emeritus) / Aebersold, Rudolf (emeritus)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02538 - Institut für Molekulare Systembiologie / Institute for Molecular Systems Biology::03663 - Aebersold, Rudolf (emeritus) / Aebersold, Rudolf (emeritus)
ethz.grant.agreementno
670821
ethz.grant.fundername
EC
ethz.grant.funderDoi
10.13039/501100000780
ethz.grant.program
H2020
ethz.date.deposited
2020-09-04T20:18:21Z
ethz.source
SCOPUS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.date.embargoend
2021-07-14
ethz.rosetta.installDate
2020-09-10T13:21:07Z
ethz.rosetta.lastUpdated
2024-02-02T14:19:41Z
ethz.rosetta.versionExported
true
ethz.COinS
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