There is growing evidence that bisphenol A (BPA), a molecule largely released in the environment, has detrimental effects on ecosystems and on human health. It acts as an endocrine disruptor targeting steroid hormone receptors, such as the estrogen receptor (ER), estrogen-related receptor (ERR) and androgen receptor (AR). BPA-derived molecules have recently been shown to interact with the AR N-terminal domain (AR-NTD), which is known to be largely intrinsically disordered. This N-terminal domain contains an 11 residue conserved domain that forms amyloid fibers upon oxidative dimerisation through its strictly conserved Cys240 residue. We investigate here the interaction of BPA, and other potential endocrine disruptors, with AR-NTD amyloid fibers using the WaterLOGSY NMR experiment. We observed a selective binding of these compounds to the amyloid fibers formed by the AR-NTD conserved region and glutamine homopolymers. This observation suggests that the high potency of endocrine disruptors may result, in part, from their ability to bind amyloid forms of nuclear receptors in addition to their cognate binding sites. This property may be exploited to design future therapeutic strategies targeting AR related diseases such as the spinal bulbar muscular atrophy or prostate cancer. The ability of NMR WaterLOGSY experiments to detect weak interactions between small ligands and amyloid fibers may prove to be of particular interest for identifying promising hit molecules.
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Univ British Columbia, Vancouver, BC V6T 1Z1, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Andersen, Raymond J.
Mawji, Nasrin R.
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Mawji, Nasrin R.
Wang, Jun
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Jun
Wang, Gang
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Gang
Haile, Simon
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Haile, Simon
Myung, Jae-Kyung
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Myung, Jae-Kyung
Watt, Kate
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h-index: 0
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Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, ScotlandBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Watt, Kate
Tam, Teresa
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Tam, Teresa
Yang, Yu Chi
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Yang, Yu Chi
Banuelos, Carmen A.
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h-index: 0
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British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Banuelos, Carmen A.
Williams, David E.
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British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Williams, David E.
McEwan, Iain J.
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Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, ScotlandBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
McEwan, Iain J.
Wang, Yuzhou
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British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Yuzhou
Sadar, Marianne D.
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机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
机构:
Univ British Columbia, Vancouver, BC V6T 1Z1, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Andersen, Raymond J.
Mawji, Nasrin R.
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Mawji, Nasrin R.
Wang, Jun
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h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Jun
Wang, Gang
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h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Gang
Haile, Simon
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Haile, Simon
Myung, Jae-Kyung
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Myung, Jae-Kyung
Watt, Kate
论文数: 0引用数: 0
h-index: 0
机构:
Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, ScotlandBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Watt, Kate
Tam, Teresa
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Tam, Teresa
Yang, Yu Chi
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Yang, Yu Chi
Banuelos, Carmen A.
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Banuelos, Carmen A.
Williams, David E.
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Williams, David E.
McEwan, Iain J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Aberdeen, Sch Med Sci, Aberdeen AB25 2ZD, ScotlandBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
McEwan, Iain J.
Wang, Yuzhou
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Canc Endocrinol, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada
Wang, Yuzhou
Sadar, Marianne D.
论文数: 0引用数: 0
h-index: 0
机构:
British Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, CanadaBritish Columbia Canc Agcy, Dept Genome Sci Ctr, Vancouver, BC V5Z 1L3, Canada