NMR WaterLOGSY Reveals Weak Binding of Bisphenol A with Amyloid Fibers of a Conserved 11 Residue Peptide from Androgen Receptor

被引:7
作者
Asencio-Hernandez, Julia [1 ]
Kieffer, Bruno [1 ]
Delsuc, Marc-Andre [1 ]
机构
[1] Univ Strasbourg, IGBMC, INSERM U596, CNRS UMR 7104, Illkirch Graffenstaden, France
来源
PLOS ONE | 2016年 / 11卷 / 09期
关键词
PROSTATE-CANCER; DISEASE; DOMAIN; AGGREGATION; DISCOVERY; TERMINUS; PROTEINS; ESTROGEN; AFFINITY; HEALTH;
D O I
10.1371/journal.pone.0161948
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页数:12
相关论文
共 31 条
  • [1] Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor
    Andersen, Raymond J.
    Mawji, Nasrin R.
    Wang, Jun
    Wang, Gang
    Haile, Simon
    Myung, Jae-Kyung
    Watt, Kate
    Tam, Teresa
    Yang, Yu Chi
    Banuelos, Carmen A.
    Williams, David E.
    McEwan, Iain J.
    Wang, Yuzhou
    Sadar, Marianne D.
    [J]. CANCER CELL, 2010, 17 (06) : 535 - 546
  • [2] Optimization of the hydrochloric acid concentration used for trifluoroacetate removal from synthetic peptides
    Andrushchenko, Valery V.
    Vogel, Hans J.
    Prenner, Elmar J.
    [J]. JOURNAL OF PEPTIDE SCIENCE, 2007, 13 (01) : 37 - 43
  • [3] Comparison of the sensitivities of WaterLOGSY and saturation transfer difference NMR experiments
    Antanasijevic, Aleksandar
    Ramirez, Benjamin
    Caffrey, Michael
    [J]. JOURNAL OF BIOMOLECULAR NMR, 2014, 60 (01) : 37 - 44
  • [4] Reversible Amyloid Fiber Formation in the N Terminus of Androgen Receptor
    Asencio-Hernandez, Julia
    Ruhlmann, Christine
    McEwen, Alastair
    Eberling, Pascal
    Nomine, Yves
    Ceraline, Jocelyn
    Starck, Jean-Philippe
    Delsuc, Marc-Andre
    [J]. CHEMBIOCHEM, 2014, 15 (16) : 2370 - 2373
  • [5] History of genetic disease - The molecular genetics of Huntington disease - a history
    Bates, GP
    [J]. NATURE REVIEWS GENETICS, 2005, 6 (10) : 766 - 773
  • [6] ANALYSIS OF THE CAG REPEAT REGION OF THE ANDROGEN RECEPTOR GENE IN A KINDRED WITH X-LINKED SPINAL AND BULBAR MUSCULAR-ATROPHY
    BELSHAM, DD
    YEE, WC
    GREENBERG, CR
    WROGEMANN, K
    [J]. JOURNAL OF THE NEUROLOGICAL SCIENCES, 1992, 112 (1-2) : 133 - 138
  • [7] Bergerat JP, 2009, HUM MUTAT
  • [8] Identification of compounds with binding affinity to proteins via magnetization transfer from bulk water
    Dalvit, C
    Pevarello, P
    Tatò, M
    Veronesi, M
    Vulpetti, A
    Sundström, M
    [J]. JOURNAL OF BIOMOLECULAR NMR, 2000, 18 (01) : 65 - 68
  • [9] WaterLOGSY as a method for primary NMR screening: Practical aspects and range of applicability
    Dalvit, C
    Fogliatto, G
    Stewart, A
    Veronesi, M
    Stockman, B
    [J]. JOURNAL OF BIOMOLECULAR NMR, 2001, 21 (04) : 349 - 359
  • [10] Huntingtin affinity for partners is not changed by polyglutamine length: aggregation itself triggers aberrant interactions
    Davranche, Aurelien
    Aviolat, Hubert
    Zeder-Lutz, Gabrielle
    Busso, Didier
    Altschuh, Daniele
    Trottier, Yvon
    Klein, Fabrice A. C.
    [J]. HUMAN MOLECULAR GENETICS, 2011, 20 (14) : 2795 - 2806