Formation of a powerful capping motif corresponding to start of "helix 12" in agonist-bound estrogen receptor-alpha contributes to increased constitutive activity of the protein

Cell Biochemistry and Biophysics
D F Skafar

Abstract

The human estrogen receptor alpha (hERalpha), a ligand-activated transcription factor, provides an excellent system for study of the conversion of a protein from inactive to active states. It binds to many different ligands which leads which to the expression or the suppression of genes in a cell-specific and promoter-specific manner, and a multitude of mutations have been identified that modify the activity of the receptor. Helix 12 is a key alpha-helix in the hormone-binding domain of the hERalpha that is directly involved in transcription activation. In this report, tyrosine 537 has been identified as the Ncap residue of helix 12 in the structures of the agonist-bound hERalpha ligand-binding domain. A capping motif has been identified in the sequence of the hERalpha that corresponds to the start of helix 12 in the fully active, agonist-bound conformation of the receptor. Analysis of the literature indicates that, with one exception, substitution of amino acids at position 537, which occur more frequently at the Ncap than tyrosine, is correlated with increased constitutive activity of the hERalpha. The results are consistent with the hypothesis that formation of a powerful capping motif that corresponds to the start of helix ...Continue Reading

Citations

Dec 6, 2005·Breast Cancer Research and Treatment·J K Hess-WilsonK E Knudsen
Nov 5, 2013·Nature Genetics·Dan R RobinsonArul M Chinnaiyan
Feb 2, 2012·International Journal of Breast Cancer·Renée de LeeuwRob Michalides
Dec 1, 2012·Journal of Receptor and Signal Transduction Research·Imen KallelAhmed Rebai
Nov 12, 2014·ACS Chemical Biology·Inga M TharunLuc Brunsveld
Nov 2, 2018·Breast Cancer Research and Treatment·Małgorzata SzostakowskaAnna Fabisiewicz
Dec 8, 2004·Endocrine Reviews·Matthew H Herynk, Suzanne A W Fuqua
Jun 11, 2020·International Journal of Molecular Sciences·Annamaria SalvatiGiorgio Giurato

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