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A novel pesticide-induced conformational state of the oestrogen receptor ligand-binding domain, detected by conformation-specific peptide binding.

Sumbayev, Vadim V., Bonefeld-Jorgensen, Eva C., Wind, Troels, Andreasen, Peter A. (2005) A novel pesticide-induced conformational state of the oestrogen receptor ligand-binding domain, detected by conformation-specific peptide binding. FEBS Letters, 579 (2). pp. 541-548. ISSN 0014-5793. (doi:10.1016/j.febslet.2004.12.025) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:10009)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
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Abstract

The diverse effects of different natural and synthetic oestrogen receptor ligands depend on induction of different receptor conformations, allowing differential interactions with other transcription factors. Different conformations of the oestrogen receptor ligand binding domains can be monitored by conformation-specific binding to peptides selected from phage-displayed peptide libraries. We now report that a group of chlorinated pesticides, including 2,4-dichlorodiphenyl-dichloroethylene, induces a peptide recognition pattern different from those induced by any one of the classical oestrogen receptor ligands. The pesticide-complexed oestrogen receptors recognized peptides reacting with the receptors complexed both with the natural oestrogen 17beta-oestradiol and with the synthetic partial antagonist 4-hydroxy-tamoxifen, respectively, indicating that the pesticide-induced conformation shares features with both the 17beta-oestradiol- and the 4-hydroxy-tamoxifen-induced conformations. The substitution H524A in the ligand binding domain conferred the pesticide-specific peptide recognition pattern and transactivation activity to the oestradiol- and the 4-hydroxy-tamoxifen-complexed receptors, indicating that one important determinant of the pesticide-induced conformation is a lack of stabilisation of any one particular receptor conformation by ligand interaction with H524, which is known to interact with both oestradiol and 4-hydroxy-tamoxifen. Thus, peptide binding analyses of oestrogen receptor conformations induced by environmental endocrine disruptors can give novel information about molecular mechanisms of oestrogen action in general. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Item Type: Article
DOI/Identification number: 10.1016/j.febslet.2004.12.025
Uncontrolled keywords: oestrogen receptor; oestrogen; endocrine disruptor; phage-displayed peptide library
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 25 Mar 2009 21:17 UTC
Last Modified: 16 Nov 2021 09:48 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/10009 (The current URI for this page, for reference purposes)

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