Skip to Main content Skip to Navigation
Journal articles

Flanking regions determine the structure of the poly-glutamine homo- repeat in huntingtin through mechanisms common among glutamine-rich human proteins

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.
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

Files

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : 2020-12-14

Please log in to resquest access to the document

Identifiers

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⟩

Share

Metrics

Record views

35