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

• Main Authors: Emmanuel Oppong, Gunter Stier, Miriam Gaal, Rebecca Seeger, Melanie Stoeck, Marc-André Delsuc, Andrew C. B. Cato, Bruno Kieffer
• Format: Article
• Language: English
• Published: MDPI AG 2017-06-01
• Series: Biomolecules
• Subjects: amyloid peptides; androgen receptor; nuclear receptor; aggregation; atomic force microscopy
• Online Access: http://www.mdpi.com/2218-273X/7/2/44

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.