Related Experiment Video

Updated: Dec 14, 2025

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

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Structural Insights of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes

Xinzhe Yu1, Ping Yi2, Ross A Hamilton2

  • 1Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Molecular Cell
|July 16, 2020
PubMed

Insights

Androgen receptor (AR) uses its N-terminal domain (NTD) to recruit coactivators, unlike other steroid receptors. Cryo-EM structures reveal AR

Area of Science:

  • Molecular biology
  • Structural biology
  • Genetics

Background:

  • Steroid receptors regulate gene transcription via coactivator recruitment.
  • Nuclear receptors (NRs) typically rely on the AF-2 domain for transcriptional activity.
  • Androgen receptor (AR) primarily uses its AF-1 domain, located in the N-terminal domain (NTD), differing from other NRs.

Purpose of the Study:

  • To elucidate the structural basis for androgen receptor (AR) mediated gene transcription.
  • To understand the unique coactivator recruitment mechanism of AR compared to other steroid receptors.
  • To investigate the role of AR's N-terminal domain (NTD) in transcriptional regulation.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structures of DNA-bound full-length AR.
  • Cryo-EM was employed to visualize the complex of AR with coactivators SRC-3 and p300.
  • Structural analysis focused on AR dimerization, coactivator interaction sites, and domain contributions.

Main Results:

  • AR exhibits a unique head-to-head and tail-to-tail dimerization mode.
  • AR directly interacts with a single SRC-3 and p300 molecule, distinct from ERα.
  • The AR N-terminal domain (NTD) is identified as the primary interface for coactivator recruitment.
  • Structural data reveals the assembly of the AR:coactivator complex.

Conclusions:

  • The AR N-terminal domain (NTD) plays a crucial role in coactivator recruitment and transcriptional regulation.
  • AR's distinct coactivator interaction mechanism, mediated by the NTD, provides insight into NR functional diversity.
  • The presented cryo-EM structures offer a foundation for understanding AR-driven transcription and potential therapeutic targeting.
Keywords:
AR dimerizationN-terminal domainN/C interactionSRC-3androgen receptorcoactivatorcomplexcryo-EMp300structure

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