An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation
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) seque...
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doaj-05cdaa36ec4b405293abeba4216e61ef2020-11-24T21:57:24ZengMDPI AGBiomolecules2218-273X2017-06-01724410.3390/biom7020044biom7020044An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine AggregationEmmanuel Oppong0Gunter Stier1Miriam Gaal2Rebecca Seeger3Melanie Stoeck4Marc-André Delsuc5Andrew C. B. Cato6Bruno Kieffer7Department of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U964, CNRS, UMR-7104, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch–Graffenstaden, FranceHeidelberg University Biochemistry Center (BZH), INF 328, D-69120 Heidelberg, GermanyInstitute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, GermanyInstitute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, GermanyInstitute for Photon Science and Synchrotron Radiation, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, GermanyDepartment of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U964, CNRS, UMR-7104, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch–Graffenstaden, FranceInstitute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, GermanyDepartment of Integrative Structural Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U964, CNRS, UMR-7104, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch–Graffenstaden, FranceThe 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.http://www.mdpi.com/2218-273X/7/2/44amyloid peptidesandrogen receptornuclear receptoraggregationatomic force microscopy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emmanuel Oppong Gunter Stier Miriam Gaal Rebecca Seeger Melanie Stoeck Marc-André Delsuc Andrew C. B. Cato Bruno Kieffer |
spellingShingle |
Emmanuel Oppong Gunter Stier Miriam Gaal Rebecca Seeger Melanie Stoeck Marc-André Delsuc Andrew C. B. Cato Bruno Kieffer An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation Biomolecules amyloid peptides androgen receptor nuclear receptor aggregation atomic force microscopy |
author_facet |
Emmanuel Oppong Gunter Stier Miriam Gaal Rebecca Seeger Melanie Stoeck Marc-André Delsuc Andrew C. B. Cato Bruno Kieffer |
author_sort |
Emmanuel Oppong |
title |
An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation |
title_short |
An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation |
title_full |
An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation |
title_fullStr |
An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation |
title_full_unstemmed |
An Amyloidogenic Sequence at the N-Terminus of the Androgen Receptor Impacts Polyglutamine Aggregation |
title_sort |
amyloidogenic sequence at the n-terminus of the androgen receptor impacts polyglutamine aggregation |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2017-06-01 |
description |
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. |
topic |
amyloid peptides androgen receptor nuclear receptor aggregation atomic force microscopy |
url |
http://www.mdpi.com/2218-273X/7/2/44 |
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