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Title: Understanding ligand binding effects on the conformation of estrogen receptor alpha-DNA complexes: a combinational quartz crystal microbalance with dissipation and surface plasmon resonance study. Author: Peh WY, Reimhult E, Teh HF, Thomsen JS, Su X. Journal: Biophys J; 2007 Jun 15; 92(12):4415-23. PubMed ID: 17384075. Abstract: Estrogen receptors are ligand-activated transcription factors that regulate gene expression by binding to specific DNA sequences. To date, the effect of ligands on the conformation of estrogen receptor alpha (ERalpha)-DNA complex remains a poorly understood issue. In our study, we are introducing the quartz crystal microbalance with dissipation monitoring (QCM-D) as a new alternative to study the conformational differences in protein-DNA complexes. Specifically, we have used QCM-D, in combination with surface plasmon resonance (SPR) spectroscopy, to monitor the binding of ERalpha to a specific DNA (estrogen response element, ERE) and a nonspecific DNA in the presence of either the agonist ligand, 17b-estradiol, the partial antagonist ligand, 4-hydroxytamoxifen, or vehicle alone. Both with presence and absence of ligand, the specific ERalpha-ERE complexes are observed to adopt a more compact conformation compared to nonspecific complexes. This observation is well correlated to the biophysical changes occurring during protein-DNA interaction shown by past structural and mechanism studies. Notably, pretreatment of ERalpha with E2 and 4OHT affects not only the viscoelasticity and conformation of the protein-DNA complex but also ERalpha binding capacity to immobilized ERE. These results affirm that ligands have remarkable effects on ERalpha-DNA complexes. Understanding these effects will provide insight into how ligand binding promotes subsequent events required for gene transcription.[Abstract] [Full Text] [Related] [New Search]