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Mol Cell. 2015 Mar 19;57(6):1047-1058. doi: 10.1016/j.molcel.2015.01.025. Epub 2015 Feb 26.

Structure of a biologically active estrogen receptor-coactivator complex on DNA.

Author information

1
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Clayton Foundation for Research, Houston, TX 77056, USA.
2
National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
3
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
4
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; National Center for Macromolecular Imaging, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: wah@bcm.edu.
5
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: berto@bcm.edu.

Abstract

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.

PMID:
25728767
PMCID:
PMC4369429
DOI:
10.1016/j.molcel.2015.01.025
[Indexed for MEDLINE]
Free PMC Article

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