Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor

TitleSide chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor
Publication TypeJournal Article
Year of Publication2019
AuthorsEscobedo, Albert, Topal Busra, Kunze Micha B. A., Aranda Juan, Chiesa Giulio, Mungianu Daniele, Bernardo-Seisdedos Ganeko, Eftekharzadeh Bahareh, Gairí Margarida, Pierattelli Roberta, Felli Isabella C., Diercks Tammo, Millet Oscar, García Jesús, Orozco Modesto, Crehuet Ramon, Lindorff-Larsen Kresten, and Salvatella Xavier
JournalNature Communication
Volume10
Issue1
Pagination2034
Date Published05/2019
ISBN Number2041-1723
Abstract

Polyglutamine (polyQ) tracts are regions of low sequence complexity frequently found in transcription factors. Tract length often correlates with transcriptional activity and expansion beyond specific thresholds in certain human proteins is the cause of polyQ disorders. To study the structural basis of the association between tract length, transcriptional activity and disease, we addressed how the conformation of the polyQ tract of the androgen receptor, associated with spinobulbar muscular atrophy (SBMA), depends on its length. Here we report that this sequence folds into a helical structure stabilized by unconventional hydrogen bonds between glutamine side chains and main chain carbonyl groups, and that its helicity directly correlates with tract length. These unusual hydrogen bonds are bifurcate with the conventional hydrogen bonds stabilizing α-helices. Our findings suggest a plausible rationale for the association between polyQ tract length and androgen receptor transcriptional activity and have implications for establishing the mechanistic basis of SBMA.

URLhttps://doi.org/10.1038/s41467-019-09923-2
Short TitleNature Communications
Highlight: 
Review: