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  4. Mutant Exon1 Huntingtin Aggregation is Regulated by T3 Phosphorylation-Induced Structural Changes and Crosstalk between T3 Phosphorylation and Acetylation at K6
 
research article

Mutant Exon1 Huntingtin Aggregation is Regulated by T3 Phosphorylation-Induced Structural Changes and Crosstalk between T3 Phosphorylation and Acetylation at K6

Chiki, Anass  
•
DeGuire, Sean M  
•
Ruggeri, Francesco S
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2017
Angewandte Chemie (International ed. in English)

Herein, we used protein semisynthesis to investigate, for the first time, the effect of lysine acetylation and phosphorylation, as well as the crosstalk between these modifications on the structure and aggregation of mutant huntingtin exon1 (Httex1). Our results demonstrate that phosphorylation at T3 stabilizes the α-helical conformation of the N-terminal 17 amino acids (Nt17) and significantly inhibits the aggregation of mutant Httex1. Acetylation of single lysine residues, K6, K9 or K15, had no effect on Httex1 aggregation. Interestingly, acetylation at K6, but not at K9 or K15, reversed the inhibitory effect of T3 phosphorylation. Together, our results provide novel insight into the role of Nt17 post-translational modifications in regulating the structure and aggregation of Httex1 and suggest that its aggregation and possibly its function(s) are controlled by regulatory mechanisms involving crosstalk between different PTMs.

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Type
research article
DOI
10.1002/anie.201611750
Web of Science ID

WOS:000399951200005

Author(s)
Chiki, Anass  
DeGuire, Sean M  
Ruggeri, Francesco S
Sanfelice, Domenico
Ansaloni, Annalisa  
Wang, Zhe-Ming
Cendrowska, Urszula  
Burai, Ritwik  
Vieweg, Sophie  
Pastore, Annalisa
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Date Issued

2017

Publisher

Wiley-Blackwell

Published in
Angewandte Chemie (International ed. in English)
Volume

56

Issue

19

Start page

5202

End page

5207

Subjects

acetylation

•

fibrils

•

Huntington's disease

•

phosphorylation

•

semisynthesis

URL

URL

http://onlinelibrary.wiley.com/doi/10.1002/anie.201611750/abstract;jsessionid=A488E9CD55C23AEB1E55351ECBA67C17.f03t04?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+and+Sunday+i.e+16th+and+17th+September+at+3%3A00+EDT+%2F+8%3A00+BST+%2F+12%3A30+IST+%2F+15%3A00+SGT+for+5+hours+and+3hours+for+essential+maintenance.+Apologies+for+any+inconvenience+caused+.
Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LMNN  
Available on Infoscience
March 28, 2017
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/136084
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