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: Escobedo, Albert, Topal, Busra, Kunze, Micha B.A., Aranda, Juan, Chiesa, Giulio, Mungianu, Daniele, Bernardo-Seisdedos, Ganeko, Eftekharzadeh, Bahareh, Gairi, Margarida, Pierattelli, Roberta, Felli, Isabella Caterina, Diercks, Tammo, Millet, Oscar, García, Jesús, Orozco, Modesto, Crehuet, Ramón, Lindorff-Larsen, Kresten, Salvatella, Xavier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/200649
Acceso en línea:http://hdl.handle.net/10261/200649
Access Level:acceso abierto
Palabra clave:Peptides
Mice
Huntington disease
HD Mouse
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. © 2019, The Author(s).

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