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Journal articles
Flanking regions determine the structure of the poly-glutamine homo- repeat in huntingtin through mechanisms common among glutamine-rich human proteins
Annika Urbanek
1
Matija Popovic
1
Anna Morató
1
Alejandro Estaña
1
Carlos Elena-Real
1
Pablo Mier
2
Aurélie Fournet
1
Frédéric Allemand
1
Stéphane Delbecq
3
Miguel Andrade-Navarro
Juan Cortés
4
Nathalie Sibille
5
Pau Bernadó
1
4
LAAS-RIS - Équipe Robotique et InteractionS
LAAS - Laboratoire d'analyse et d'architecture des systèmes
Carlos A Elena-Real 1
Author
Pablo Mier 2
Author
Aurélie Fournet 1
Author
Frédéric Allemand 1
Author
Stéphane Delbecq 3
Author IdHAL : stephane-delbecq
Miguel A Andrade-Navarro
Author
Juan Cortés 4
Author Employer institution : Équipe Robotique et InteractionS IdHAL : juan-cortes ResearcherId : http://www.researcherid.com/rid/F-7545-2019 ORCID : https://orcid.org/0000-0002-4660-0306
Nathalie Sibille 5
Author
Pau N Bernadó 1
Author
1
CBS - Centre de Biochimie Structurale [Montpellier] (29 rue de Navacelles 34090 Montpellier Cedex - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5048 (France)
- UM - Université de Montpellier (163 rue Auguste Broussonnet - 34090 Montpellier - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1054 (101, rue de Tolbiac, 75013 Paris - France)
2
JGU - Johannes Gutenberg - Universität Mainz (55099 Mainz - Germany)
3
LBCM - Vaccination Antiparasitaire : Laboratoire de Biologie Cellulaire et Moléculaire (5 Boulevard Henri IV 34000 Montpellier - France)
- UM1 - Université Montpellier 1 : EA4558 (5, boulevard Henri IV - CS 19044 - 34967 Montpellier cedex - France)
- UM - Université de Montpellier : EA 4558 (163 rue Auguste Broussonnet - 34090 Montpellier - France)
4
LAAS-RIS - Équipe Robotique et InteractionS ( - France)
- LAAS - Laboratoire d'analyse et d'architecture des systèmes (7 Av du colonel Roche 31077 TOULOUSE CEDEX 4 - France)
- Toulouse INP - Institut National Polytechnique (Toulouse) (France)
- Université Fédérale Toulouse Midi-Pyrénées (41 Allée Jules Guesde, 31000 Toulouse - France)
- INSA Toulouse - Institut National des Sciences Appliquées - Toulouse (135, avenue de Rangueil - 31077 Toulouse cedex 4 - France)
- UT3 - Université Toulouse III - Paul Sabatier (118 route de Narbonne - 31062 Toulouse - France)
- Université Fédérale Toulouse Midi-Pyrénées (41 Allée Jules Guesde, 31000 Toulouse - France)
- CNRS - Centre National de la Recherche Scientifique : UPR8001 (France)
- UT1 - Université Toulouse 1 Capitole (2 rue du Doyen-Gabriel-Marty - 31042 Toulouse Cedex 9 - France)
- UT2J - Université Toulouse - Jean Jaurès (5 allées Antonio Machado - 31058 Toulouse Cedex 9 - France)
- Toulouse INP - Institut National Polytechnique (Toulouse) (France)
5
UGSF - Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (Université de Lille Sciences et technologies - UMR8576 CNRS Cité Scientifique - Bâtiment C9 F-59655 Villeneuve d’Ascq Cedex - France)
- Université de Lille (Lille - France)
- CNRS - Centre National de la Recherche Scientifique : UMR8576 (France)
- INRA - Institut National de la Recherche Agronomique : USC1409 (France)
Abstract : The causative agent of Huntington's disease, the poly-Q homo-repeat in the N-terminal region of huntingtin (httex1), is flanked by a 17-residue-long fragment (N17) and a proline-rich region (PRR), which promote and inhibit the aggregation propensity of the protein, respectively, by poorly understood mechanisms. Based on experimental data obtained from site-specifically labeled NMR samples, we derived an ensemble model of httex1 that identified both flanking regions as opposing poly-Q secondary structure promoters. While N17 triggers helicity through a promiscuous hydrogen bond network involving the side chains of the first glutamines in the poly-Q tract, the PRR promotes extended conformations in neighboring glutamines. Furthermore, a bioinformatics analysis of the human proteome showed that these structural traits are present in many human glutamine-rich proteins and that they are more prevalent in proteins with longer poly-Q tracts. Taken together, these observations provide the structural bases to understand previous biophysical and functional data on httex1.
Document type :
Journal articles
Complete list of metadatas
https://hal.laas.fr/hal-02893075
Contributor : Juan Cortés <>
Submitted on : Wednesday, July 8, 2020 - 8:12:27 AM
Last modification on : Tuesday, September 8, 2020 - 4:34:35 PM
Contributor : Juan Cortés <>
Submitted on : Wednesday, July 8, 2020 - 8:12:27 AM
Last modification on : Tuesday, September 8, 2020 - 4:34:35 PM
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To satisfy the distribution rights of the publisher, the document is embargoed until : 2020-12-14Please log in to resquest access to the document
- Urbanek_etal_SI_rev_H16_HAL.pdf Embargoed until : 2020-12-14
Identifiers
- HAL Id : hal-02893075, version 1
- DOI : 10.1016/j.str.2020.04.008
Collections
LAAS | UNIV-TLSE3 | INRA | UT1-CAPITOLE | UNIV-TLSE2 | UNIV-MONTPELLIER | INSA-TOULOUSE | LAAS-ROBOTIQUE | UNIV-LILLE | LAAS-RIS | INSA-GROUPE | CNRS | INRAE | BS
Citation
Annika Urbanek, Matija Popovic, Anna Morató, Alejandro Estaña, Carlos Elena-Real, et al.. Flanking regions determine the structure of the poly-glutamine homo- repeat in huntingtin through mechanisms common among glutamine-rich human proteins. Structure, Elsevier (Cell Press), 2020, 28 (7), pp.733-746.e5. ⟨10.1016/j.str.2020.04.008⟩. ⟨hal-02893075⟩
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