Structure of a biologically active estrogen receptor-coactivator complex on DNA.
Estrogen receptor (ER/ESR1) is a transcription factor critical for development, reproduction, metabolism, and cancer. ER function hinges on its ability to recruit primary and secondary coactivators, yet structural information on the full-length receptor-coactivator complex to complement preexisting and sometimes controversial biochemical information is lacking. Here, we use cryoelectron microscopy (cryo-EM) ... to determine the quaternary structure of an active complex of DNA-bound ERα, steroid receptor coactivator 3 (SRC-3/NCOA3), and a secondary coactivator (p300/EP300). Our structural model suggests the following assembly mechanism for the complex: each of the two ligand-bound ERα monomers independently recruits one SRC-3 protein via the transactivation domain of ERα; the two SRC-3s in turn bind to different regions of one p300 protein through multiple contacts. We also present structural evidence for the location of activation function 1 (AF-1) in a full-length nuclear receptor, which supports a role for AF-1 in SRC-3 recruitment.
Mesh Terms:
Binding Sites, Cryoelectron Microscopy, DNA, E1A-Associated p300 Protein, Estrogen Receptor alpha, Histone Acetyltransferases, Humans, Multiprotein Complexes, Nuclear Receptor Coactivator 3, Protein Conformation, Protein Structure, Tertiary, Response Elements
Binding Sites, Cryoelectron Microscopy, DNA, E1A-Associated p300 Protein, Estrogen Receptor alpha, Histone Acetyltransferases, Humans, Multiprotein Complexes, Nuclear Receptor Coactivator 3, Protein Conformation, Protein Structure, Tertiary, Response Elements
Mol. Cell
Date: Mar. 19, 2015
PubMed ID: 25728767
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