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An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation

Oppong, Emmanuel; Stier, Gunter; Gaal, Miriam; Seeger, Rebecca; Stoeck, Melanie; Delsuc, Marc-André; Cato, Andrew C. B.; Kieffer, Bruno

Abstract:
The human androgen receptor (AR) is a ligand inducible transcription factor that harbors an amino terminal domain (AR-NTD) with a ligand-independent activation function. AR-NTD is intrinsically disordered and displays aggregation properties conferred by the presence of a poly-glutamine (polyQ) sequence. The length of the polyQ sequence as well as its adjacent sequence motifs modulate this aggregation property. AR-NTD also contains a conserved KELCKAVSVSM sequence motif that displays an intrinsic property to form amyloid fibrils under mild oxidative conditions. As peptide sequences with intrinsic oligomerization properties are reported to have an impact on the aggregation of polyQ tracts, we determined the effect of the KELCKAVSVSM on the polyQ stretch in the context of the AR-NTD using atomic force microscopy (AFM). Here, we present evidence for a crosstalk between the amyloidogenic properties of the KELCKAVSVSM motif and the polyQ stretch at the AR-NTD.


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Institut für Photonenforschung und Synchrotronstrahlung (IPS)
Publikationstyp Zeitschriftenaufsatz
Jahr 2017
Sprache Englisch
Identifikator DOI: 10.3390/biom7020044
ISSN: 2218-273X
URN: urn:nbn:de:swb:90-717569
KITopen ID: 1000071756
HGF-Programm 47.01.01; LK 01
Erschienen in Biomolecules
Band 7
Heft 2
Seiten 44
Lizenz CC BY 4.0: Creative Commons Namensnennung 4.0 International
Bemerkung zur Veröffentlichung Gefördert durch den KIT-Publikationsfonds
Schlagworte amyloid peptides; androgen receptor; nuclear receptor; aggregation; atomic force microscopy
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