Side chain to main chain hydrogen bonds stabilize a polyglutamine helix in a transcription factor.
Bulbo-Spinal Atrophy, X-Linked
/ genetics
Circular Dichroism
Glutamine
/ chemistry
Humans
Hydrogen
/ chemistry
Hydrogen Bonding
Magnetic Resonance Spectroscopy
Molecular Dynamics Simulation
Mutation
Peptides
/ chemistry
Protein Aggregates
/ genetics
Protein Conformation, alpha-Helical
/ genetics
Receptors, Androgen
/ chemistry
Transcription Factors
/ chemistry
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 05 2019
02 05 2019
Historique:
received:
13
02
2019
accepted:
09
04
2019
entrez:
4
5
2019
pubmed:
3
5
2019
medline:
14
6
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31048691
doi: 10.1038/s41467-019-09923-2
pii: 10.1038/s41467-019-09923-2
pmc: PMC6497633
doi:
Substances chimiques
AR protein, human
0
Peptides
0
Protein Aggregates
0
Receptors, Androgen
0
Transcription Factors
0
Glutamine
0RH81L854J
polyglutamine
26700-71-0
Hydrogen
7YNJ3PO35Z
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2034Subventions
Organisme : European Research Council
ID : 648201
Pays : International
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