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

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...

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Detalles Bibliográficos
Autores principales: Escobedo, 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, Salvatella, Xavier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497633/
https://www.ncbi.nlm.nih.gov/pubmed/31048691
http://dx.doi.org/10.1038/s41467-019-09923-2
Descripción
Sumario: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.