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

Molecular Cell
Xinzhe YuBert W O'Malley

Abstract

Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (NR) transcriptional activity. In contrast to other steroid receptors, such as ERα, the activation function of androgen receptor (AR) is largely dependent on its ligand-independent AF-1 located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different AF domain from other receptors despite that NRs share similar domain organizations. Here, we present cryoelectron microscopy (cryo-EM) structures of DNA-bound full-length AR and its complex structure with key coactivators, SRC-3 and p300. AR dimerization follows a unique head-to-head and tail-to-tail manner. Unlike ERα, AR directly contacts a single SRC-3 and p300. The AR NTD is the primary site for coactivator recruitment. The structures provide a basis for understanding assembly of the AR:coactivator complex and its domain contributions for coactivator assembly and transcriptional regulation.

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Citations

Jan 20, 2021·Nature Medicine·Theresa E HickeyWayne D Tilley
Jan 30, 2021·The Biochemical Journal·Martin StortzValeria Levi
Jan 2, 2021·The Journal of Biological Chemistry·Irfan AsanganiTrevor M Penning
Jan 12, 2021·The Journal of Biological Chemistry·Irfan AsanganiTrevor M Penning
Apr 17, 2021·Genome Biology·Anil Panigrahi, Bert W O'Malley
May 1, 2021·Biomolecules·Elizabeth Martínez-RojoJesica Escobar-Cabrera
Jun 2, 2021·Essays in Biochemistry·Ping YiBert W O'Malley
Dec 15, 2020·Seminars in Cancer Biology·Joan Font-DíazAnnabel F Valledor
Sep 22, 2021·Journal of Molecular Biology·Timothy S StrutzenbergPatrick R Griffin
Oct 29, 2021·Biochemical Society Transactions·Filipp FrankXu Liu

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